12
Review Article Recent Research Trends and Future Prospects in Nanozymes Ho Yun Shin, 1 Tae Jung Park, 2 and Moon Il Kim 1 1 Department of BioNano Technology, Gachon University, 1342 Seongnamdae-ro, Sujeong-gu, Seongnam, Gyeonggi 461-701, Republic of Korea 2 Department of Chemistry, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 156-756, Republic of Korea Correspondence should be addressed to Tae Jung Park; [email protected] and Moon Il Kim; [email protected] Received 21 July 2015; Accepted 17 November 2015 Academic Editor: Xuping Sun Copyright © 2015 Ho Yun Shin et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Recently, nanomaterial-based enzyme mimetics (nanozymes) have attracted enormous interest. ey exhibit unique advantages such as excellent robustness, stability, and low-cost production with easy scale-up, which are critically needed as an alternative to natural enzymes. ese nanozymes exhibit natural enzyme-like activity and have been applied to various kinds of detection and treatment methods for biomolecules such as DNA, proteins, cells, and small molecules including glucose. To highlight progress in the field of nanozymes, this review discusses recent nanozyme-based research results and their applications for the development of novel biosensor, immunoassay, cancer diagnostics, therapeutics, and environmental engineering technologies. Current challenges and future prospects of nanozymes for widespread use in biotechnology are also discussed. 1. Introduction Early diagnosis of diseases is an area of growing importance for the medical community. e early detection of diseases helps improve therapeutic decision-making, which decreases the severity of illness and length of hospital stay. Accordingly, a number of biosensing techniques have been developed for rapid, reliable, and sensitive detection of biomolecules that can be used as indicators of disease. Among various biosensing methods for diagnosing human diseases, nat- ural enzymes such as horseradish peroxidases have been frequently used for bioassay, as they can catalyze various colorimetric reactions in the presence of specially designed substrates, and they display good sensitivity and selectivity towards the target molecules [1]. In spite of their novel catalytic efficiency, natural enzymes have critical limitations for industrial application, such as low stability in harsh conditions (temperature and pH) and relatively high costs for preparation, purification, and storage. erefore, over the past few decades, researchers have made an intense effort to develop artificial enzymes for a wide range of applications. For example, chemical complexes based on cyclodextrin [2], porphyrin [3, 4], hemin [5, 6], hematin [7], and specially designed biomolecules in the form of nucleic acids and proteins have been successfully used to mimic the catalytic activity of natural enzymes [8]. In this regard, Fe 3 O 4 magnetic nanoparticles (MNPs) have been found to exhibit intrinsic peroxidase activity [9]. is remarkable discovery opens up the way for a new class of enzyme mimetics. To date, various nanostructured materials have been reported to possess intrinsic enzymatic activity, including Fe 3 O 4 magnetic nanoparticles (MNPs) [9], plat- inum nanoparticles (Pt NPs) [10–12], cerium oxide nanopar- ticles (CeO 2 NPs) [13], gold nanoparticles (Au NPs) [14–16], copper oxide nanoparticles (CuO NPs) [17], BiFeO 3 nanopar- ticles [18], CoFe 2 O 4 nanoparticles [19–21], FeS and FeSe nanoparticles [22], graphene oxide [23], single-wall carbon nanotubes [24], and hemin-graphene hybrid nanosheets [25]. Herein, we name these nanomaterials which have enzyme- like catalytic activity “nanozymes.” In contrast to natural enzymes, nanozymes are inherently robust, stable in harsh conditions (pH and temperature), and easy to mass-produce with simple scale-up. ese advantages make them promising candidates for analytical and environmental applications [26]. In this paper, we present a comprehensive review of recent research on nanozymes and their applications categorized by representative fields of application, such as biosensor, Hindawi Publishing Corporation Journal of Nanomaterials Volume 2015, Article ID 756278, 11 pages http://dx.doi.org/10.1155/2015/756278

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Page 1: Review Article Recent Research Trends and Future …downloads.hindawi.com/journals/jnm/2015/756278.pdfnovel biosensor, immunoassay, cancer diagnostics, therapeutics, and environmental

Review ArticleRecent Research Trends and Future Prospects in Nanozymes

Ho Yun Shin1 Tae Jung Park2 and Moon Il Kim1

1Department of BioNano Technology Gachon University 1342 Seongnamdae-ro Sujeong-gu SeongnamGyeonggi 461-701 Republic of Korea2Department of Chemistry Chung-Ang University 84 Heukseok-ro Dongjak-gu Seoul 156-756 Republic of Korea

Correspondence should be addressed to Tae Jung Park tjparkcauackr and Moon Il Kim moonilgachonackr

Received 21 July 2015 Accepted 17 November 2015

Academic Editor Xuping Sun

Copyright copy 2015 Ho Yun Shin et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Recently nanomaterial-based enzyme mimetics (nanozymes) have attracted enormous interest They exhibit unique advantagessuch as excellent robustness stability and low-cost production with easy scale-up which are critically needed as an alternative tonatural enzymes These nanozymes exhibit natural enzyme-like activity and have been applied to various kinds of detection andtreatment methods for biomolecules such as DNA proteins cells and small molecules including glucose To highlight progress inthe field of nanozymes this review discusses recent nanozyme-based research results and their applications for the development ofnovel biosensor immunoassay cancer diagnostics therapeutics and environmental engineering technologies Current challengesand future prospects of nanozymes for widespread use in biotechnology are also discussed

1 Introduction

Early diagnosis of diseases is an area of growing importancefor the medical community The early detection of diseaseshelps improve therapeutic decision-making which decreasesthe severity of illness and length of hospital stay Accordinglya number of biosensing techniques have been developedfor rapid reliable and sensitive detection of biomoleculesthat can be used as indicators of disease Among variousbiosensing methods for diagnosing human diseases nat-ural enzymes such as horseradish peroxidases have beenfrequently used for bioassay as they can catalyze variouscolorimetric reactions in the presence of specially designedsubstrates and they display good sensitivity and selectivitytowards the target molecules [1] In spite of their novelcatalytic efficiency natural enzymes have critical limitationsfor industrial application such as low stability in harshconditions (temperature and pH) and relatively high costsfor preparation purification and storage Therefore over thepast few decades researchers have made an intense effort todevelop artificial enzymes for a wide range of applicationsFor example chemical complexes based on cyclodextrin [2]porphyrin [3 4] hemin [5 6] hematin [7] and speciallydesigned biomolecules in the form of nucleic acids and

proteins have been successfully used to mimic the catalyticactivity of natural enzymes [8]

In this regard Fe3O4magnetic nanoparticles (MNPs)

have been found to exhibit intrinsic peroxidase activity [9]This remarkable discovery opens up the way for a new class ofenzyme mimetics To date various nanostructured materialshave been reported to possess intrinsic enzymatic activityincluding Fe

3O4magnetic nanoparticles (MNPs) [9] plat-

inum nanoparticles (Pt NPs) [10ndash12] cerium oxide nanopar-ticles (CeO

2NPs) [13] gold nanoparticles (Au NPs) [14ndash16]

copper oxide nanoparticles (CuONPs) [17] BiFeO3nanopar-

ticles [18] CoFe2O4nanoparticles [19ndash21] FeS and FeSe

nanoparticles [22] graphene oxide [23] single-wall carbonnanotubes [24] and hemin-graphene hybrid nanosheets [25]Herein we name these nanomaterials which have enzyme-like catalytic activity ldquonanozymesrdquo In contrast to naturalenzymes nanozymes are inherently robust stable in harshconditions (pH and temperature) and easy to mass-producewith simple scale-upThese advantagesmake thempromisingcandidates for analytical and environmental applications[26]

In this paper we present a comprehensive review of recentresearch on nanozymes and their applications categorizedby representative fields of application such as biosensor

Hindawi Publishing CorporationJournal of NanomaterialsVolume 2015 Article ID 756278 11 pageshttpdxdoiorg1011552015756278

2 Journal of Nanomaterials

NanozymesImmunoassay

Environmental engineering

Biosensor

Cancer diagnostics and therapy

Figure 1 Awide range of applications in the field of nanozymesThe images of nanomaterials in the center ring represent (clockwise from topleft) Fe

3O4nanoparticle CeO

2nanoparticle graphene oxide andAunanoparticle which are the typical nanomaterials exhibiting enzyme-like

activities

immunoassay cancer diagnostics therapeutics and environ-mental engineering We also provide challenges and researchtrends in the emerging nanozyme research field (Figure 1)

2 Fundamentals of Nanozymes

Due to the absence of an active site in nanozymes where onlya specific substrate molecule binds and undergoes a chem-ical reaction researchers have developed various strategiesto endow nanozymes with specificity to target moleculesThe most representative strategies can be divided betweenthe oxidase-coupled method and the surface-modificationmethod In the oxidase-coupled method nanozymes withperoxidase-like activity gain their specificity by being coupledwith oxidase which generatesH

2O2as a product of a catalytic

reaction which occurs only in the presence of the targetmolecule Peroxidase-like nanozymes subsequently catalyzethe oxidation of colorimetric substrates with the resultingH2O2 For the surface-modification method an antibody

is generally conjugated on the surface of the nanozyme toprovide specificity toward antigen molecules mostly in thecolorimetric immunoassay system By conjugation of theantibody specific to the target antigen on the surface ofthe nanozyme the nanozyme can act as a target-specificprobe generating a colorimetric signal in the presence of thecolorimetric substrate andH

2O2 In the samemanner ligand-

conjugated nanozymes can specifically bind to target recep-tors and produce a colorimetric signal when the targetedmolecules bind on the nanozymesrsquo surface Aptamers areattracting interest in the fields of therapeutics and diagnostics

and are becoming promising candidates for use in givingspecificity to nanozyme-based biosensors

The intrinsic enzyme-like activities of nanozymes aregenerally believed to be produced by atoms present on thesurface as well as in the nanozymersquos inside core Thus theatomic composition of nanozymes is the most importantfactor in determining their catalytic activity although otherfactors such as size morphology surface coating and mod-ification pH and temperature can also have an impact[8] Based on the type of composition nanozymes can bedistributed into three categories metal oxide-based metal-based and carbon-based nanozymes

21 Metal Oxide-Based Nanozymes Metal oxide nanopar-ticles have been widely used in the field of biomedicalapplications such as biosensor targeted drug delivery tis-sue repair immunoassay and contrast agents in magneticresonance imaging (MRI) and cell separation [27] Sincemetal oxide nanoparticles are commonly considered chem-ically and biologically inert additional surface engineeringand subsequent conjugation with functional substances arerequired to endowmetal oxide nanoparticles with functional-ity Recently inspired by the notable discovery of the intrinsiccatalytic activity of MNP as a peroxidase [9] metal oxide-type nanozymes have attracted great interest with a largenumber of papers discussing newly reported enzyme-likeactivities of these nanomaterials A variety of metal oxide-based nanozymes have been discovered to possess enzyme-like catalytic activities (peroxidase catalase and superoxidedismutase (SOD)) including MNPs [9] CeO

2NPs [13]

Journal of Nanomaterials 3

cobalt oxide nanoparticles (Co3O4NPs) [28] manganese

dioxide nanoparticles (MnO2NPs) [29] vanadiumpentoxide

nanoparticles (V2O5NPs) [30] and CuONPs [31] Generally

metal oxide-based nanozymes with peroxidase-like activityhave been those most widely investigated by researchersowing to their convenience for constructing amperometricand colorimetric detection systems by utilizing the capabilityof peroxidase to catalyze certain substrates which generatethe corresponding electric and colorimetric signal in thepresence of hydrogen peroxide (H

2O2) Herein we focus

on colorimetric detection systems utilizing peroxidase-likenanozymes and associated applications

22 Metal-Based Nanozymes Metal-based nanozymes suchas Au NPs and Pt NPs have been discovered to pos-sess the catalytic activities of oxidase peroxidase catalaseand SOD In addition to the single nanoparticle systemmentioned above nanocomposites which combine a metal-based nanozyme with other nanozymes have been alsointensively developed including Fe

3O4-graphene oxide (GO)

[32] Fe3O4-Pt [33] Au-Pt [34] and GO-Fe

3O4-Pt [35]

nanocomposites Surprisingly it was reported that metal-based nanozymes often exhibit synergistic effects whichsignificantly enhance catalytic performance when coupledwith other nanozymes as a composite [33]

23 Carbon-Based Nanozymes Carbon-based nanozymessuch as fullerene carbon nanotube graphene oxide andcarbon dot are also attracting great interest owing to theirunique enzyme-mimicking activities [23ndash25 36ndash43] Theyhave been found to possess peroxidase and SOD-mimickingabilities and are widely utilized as signaling agents forsignal amplification and detection of analytes in the field ofbiosensors and immunoassays

3 Recent Applications

31 Biosensors In recent time horseradish peroxidase(HRP) which can catalyze the oxidation of a variety ofsubstrates by H

2O2 has been one of the most commonly

used enzymes for the construction of biosensors In spiteof its high catalytic efficiency HRP-based biosensors havecritical problems in that the catalytic activity of HRP is proneto degradation in long-term storage and harsh conditionsthereby leading to errors in the process of sensing To solvethis problem a peroxidase-like nanozyme which is highlyrobust against environmental conditions is utilized in placeof HRP providing a cost-effective method of fabrication ofbiosensors

311 H2O2 Detection H2O2 detection plays an essential rolein the fields of biologymedicine environmental engineeringand food industry Since H

2O2 a product of an incompletely

reduced metabolite of oxygen is generated as a by-productof various biological pathways and is a contaminant inseveral industrial products and wastes H

2O2detection is of

practical importance in the field of biosensors With sub-stantial progress in biosensing technology various methodsfor H2O2detection have been reported Among them is the

colorimetric signal readout strategy based on a redox reac-tion between HRP and colorimetric substrates such as 221015840-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS)and 331015840551015840-tetramethylbenzidine (TMB) This strategy hasbeen actively developed due to its high sensitivity selectiv-ity and simplicity for detecting H

2O2 However since the

colorimetric detection method using HRP has problems oflow stability and high cost nanozymes showing peroxidase-like activity have been intensively utilized to resolve thesedrawbacks Beginning with the remarkable discovery thatMNPs exhibit intrinsic peroxidase-like activity [9] manyresearchers have focused on the development of novel H

2O2

detection methods employing various nanozymes Here wediscuss recent applications of various nanozymes in H

2O2

detectionAfter Yanrsquos report H

2O2detection methods with MNPs

(used as peroxidase-like nanozymes) were further developedby Wei and Wang [44] This research outlined a colorimetricdetection method for H

2O2 in which MNPs were used to

catalyze the oxidation of ABTS in the presence of H2O2

The catalytic oxidation of ABTS with H2O2generates green-

colored products by which H2O2can be detected by the

naked eyeThey noted that ABTS could be oxidized by H2O2

in the absence of any catalysts but demonstrated that thepresence ofMNPs gave a 320 higher response of absorptionspectra when compared with the absence of MNPs Not onlythe peroxidase-like catalytic activity of Fe

3O4MNPs but also

their high stability in rough conditions (pH and temperature)was confirmed with additional investigations

Based on the colorimetric detection method abovemany approaches have proceeded by varying the colori-metric substrates and nanozymes used NN-Dimethyl-p-phenylenediamine sulfate (DPD) was used as a colorimetricsubstrate in place of ABTS [45] The DPD-MNPs analyticalsystem showed several advantages (lower operating temper-ature and detection limit and higher sensitivity) over thesystem using ABTS because DPD is more easily oxidized byH2O2than ABTS and because oxidized DPD (DPD+) pro-

duces a colored product with a strong absorption maximumat 550 nm Aside from the signal-on colorimetric methodabove Jiangrsquos group has developed a new type of fluorescencemethod using rhodamine B (RhB) as a substrate [46] Inthis method MNPs catalyze H

2O2to form the radical OH

which can oxidize RhB to form colorless and nonfluorescentproducts In short the more the H

2O2exists the weaker the

fluorescence intensity of RhB isOther nanozymes have been also reported to detect

H2O2 Au NPs have been discovered to possess intrinsic

peroxidase-like activity [47] Caorsquos studies reported thatpositively charged Au NPs can catalyze the oxidation of TMBby H2O2 Carboxyl-modified graphene oxide was shown to

possess intrinsic peroxidase-like activity that can catalyze thereaction of TMB in the presence of H

2O2to produce a blue-

color reaction [23] Concentrations as low as 5 times 10minus8mol Lminus1H2O2were detected with a linear range from 5 times 10minus8 to 1 times

10minus6mol Lminus1

312 Glucose Detection Peroxidase-like nanozymes coupledwith glucose oxidase (GOx) have been frequently employed

4 Journal of Nanomaterials

in the construction of glucose biosensors Wang et al devel-oped a colorimetric glucose detection platform by combiningthe catalytic oxidation of glucose with GOx and the catalyticreaction of ABTS withMNPs [48] Glucose concentrations aslow as 30 120583M were detected with a linear range from 50 120583Mto 1mM in this study

There have been several reports of an electrochemi-cal biosensing platform using GOx-coupled nanozymes Ahighly efficient and robust electrochemical biosensing strat-egy employing a nanocomposite harboring GOx-couplednanozymes was developed by our group [49] In this reportMNPs and GOx were entrapped in the pores of mesoporouscarbon in which GOx immobilized in the nanocompositegenerates H

2O2which then is directly reduced to H

2O

with the electrocatalytic reduction mediated by MNPs Thissystem showed a linear range of (05 to 10) times 10minus3M and adetection limit of 02 times 10minus3M

313 Oxidase-Coupled Methods (Except Glucose Oxidase)On the basis of the mechanism of glucose detection aboveseveral different oxidases have also been coupled withnanozymes for the fabrication of biosensing platforms Ananostructured multicatalyst system consisting of MNPsand cholesterol oxidase entrapped in large-pore-sized meso-porous silica has been developed for convenient colorimetricdetection of cholesterol [50] This multicatalyst system iscomposed of MNPs incorporated in the wall of mesocellularsilica pores forming magnetic mesoporous silica (MMS)and cholesterol oxidases In this system cholesterol oxidaseimmobilized in the MMS promotes a reaction with choles-terol to generate H

2O2 which subsequently activates MNPs

in the mesocellular silica pores to convert a colorimetric sub-strate into a colored product The result of this investigationshows the cholesterol oxidase-coupled method to have highselectivity and sensitivity (limit of detection LOD of 5120583Min the linear range from 10 to 250 120583M) for the detection ofcholesterol A colorimetricmethod for detection of galactosewhich utilizes a nanostructured multicatalyst system consist-ing of MNPs and galactose oxidase has also been reported[51] The clinical applicability of this multicatalytic systemwas successfully evaluated as a promising analytical tool todiagnose galactosemia by determining the concentration ofgalactose eluted from the dried blood specimens provided byclinical hospitals

Apart from the above oxidases alcohol oxidase has beenused in a colorimetric biosensor for quantification of ethanoland methanol [52] The nanocomposite system utilizingalcohol oxidase entrapped in mesocellular silica with MNPsprovided a rapid and convenient platform for analysis ofalcohol with high stability and reusability It showed a linearconcentration range from 100 to 500120583M with a detectionlimit as low as 25 120583M

314 OtherMethods Recently peroxidase-mimicking nano-materials such as MNPs CeO

2NPs and Au NPs [15] have

been employed for new methods of DNA detection A label-free colorimetric detection method for nucleic acids hasbeen developed [53] In this method the target DNA inthe sample which is amplified by polymerase chain reaction

(PCR) is directly adsorbed on the surface of the MNPs dueto electrostatic interactions between the negatively chargedphosphate backbone and the positively charged surface of theNPs thereby inducing a shielding effect against colorimetricsubstrate binding to MNPs The peroxidase activity of MNPswill decrease due to the DNA-induced shielding so thatthe intensity of the color signal will also be significantlyreduced Using this detection method researchers succes-sively detectedChlamydia trachomatis in humanurine whichis one of the common bacteria causing sexually transmitteddisease (STD) [54 55] CeO

2NPs were also employed in a

label-free colorimetric method for detecting C trachomatisand this method provided ultrafast detection of the targetnucleic acid (target nucleic acids can be determined withina few minutes) [56]

A novel biosensing format using aptamers has been devel-oped by several researchers based on the fact that aptamerswhich are ssDNA or ssRNA that can specifically bind to atarget can replace antibodies for the specific recognition oftarget molecules A method using chitosan-modified MNPsconjugated with thrombin aptamers was reported by Zhangrsquosgroup [57] They constructed a sandwich-type assay for thedetection of thrombin with two thrombin aptamers Thisaptamer-based assay showed a linear detection range from 1to 100 nM and a detection limit of 1 nM of thrombin

32 Immunoassays Immunoassays have been used in hos-pitals laboratory medicine and research to improve thehealth and well-being of humans and animals Informationgained by clinical immunoassay testing has shortened thelength of hospital stays and decreased the severity of illnessby identifying and assessing the progression of diseasethereby leading to improved therapeutic choices In lifescience research immunoassays are used in the study ofbiological systems for tracking different proteins hormonesand antibodies In industry immunoassays are used to detectcontaminants in food and water and in quality control tomonitor specific molecules used during product processingHowever themost commonly used enzymes in immunoassayinclude horseradish peroxidase and alkaline phosphatase[58ndash62] which lose their enzymatic activities gradually overlong-term storage [63] To overcome these limits variousstudies on replacing natural enzymes have been reported andconsequently novel types of immunoassay using nanozymesin place of HRP have been developed

321 Sandwich or Antigen-Down Type Immunoassays Gaoand coworkers reported an immunoassay using chitosan-modified MNPs (CS-MNPs) as a replacement for HRP in thetraditional immunoassay [63] They provided protocols forantigen-down and sandwich immunoassays with CS-MNPsand detected mouse IgG and carcinoembryonic antigen(CEA) respectively Chitosan modified on the surface ofMNPs prevented aggregation of MNPs so that MNPs wereeasily dispersed in aqueous solutions Meanwhile aminogroups in the chitosan provided a convenient site for covalentlinking of antibodies to MNPs thereby replacing the linkageof HRP-conjugated antibodies to CS-MNP-conjugated anti-bodies in the immunoassay Capture-detection immunoassay

Journal of Nanomaterials 5

was also developed to detect CEA by employing themagneticproperties of CS-MNPs which facilitate capturing separat-ing and enriching antigens as well as redispersing the MNPaggregation in solution

Zhang and coworkers reported a novel immunoassayutilizing Prussian blue modified 120574-Fe

2O3NPs [64] Prus-

sian blue a dark blue pigment with the idealized formulaFe7(CN)18 was modified on the surface of 120574-Fe

2O3NPs due

to its excellent electrochemical behavior that accelerated elec-tron transfer and its catalytic properties that could catalyzethe reduction of H

2O2 Prussian blue modified 120574-Fe

2O3NPs

(PBMNPs) were next conjugated with staphylococcal proteinA (SPA) to bind to IgG immobilized in the well so thatPBMNPs could derive a colorimetric reaction in the presenceof TMB and H

2O2

Ferritins nanoscale globular protein cages encapsulatinga ferric core were used in immunoassay in Tang et alrsquos study[65] In this study ferritin showed a thermally stable and pH-tolerable enzyme-mimetic activity derived from the ferricnanocore of ferritin Two forms of immunoassay systemswere constructed antigen-down type and sandwich typeAvidin was selected as the target molecule of the antigen-down immunoassay and nitrated human ceruloplasmin asthe target molecule of the sandwich-type immunoassayTheyalso reported that the ferritins could be utilized in analyticalapplications such as H

2O2assay In their assay ferritin

oxidizes the p-HPPA in the presence of H2O2to generate

a fluorescent product This ferritin-based H2O2assay shows

a detection limit of 016 120583M and a linear detection range of40 120583M which is one-order higher sensitivity with a broaderlinear response range

Immunoassay systems for detection of rotavirus andbreast cancer have been developed [66] in which MNPsare conjugated to antibodies against rotaviruses and humanepidermal growth factor receptor 2 (HER2) In this sys-tem sandwich-type and antigen-down type immunoassaywere used to detect rotavirus and HER2 respectively Forthe detection of rotavirus rotavirus antibodies were firstimmobilized in a well and rotavirus bound to the immo-bilized antibody Subsequently MNP-conjugated antibodies(MNP-Abs) were added to the well in order to bind tocaptured rotaviruses Finally the peroxidase substrate TMBwas changed into blue-colored products in the presence ofH2O2 An antigen-down immunoassay system was used in

the case of breast cell detection which did not require priorimmobilization of antibodies in the bare well surface Breastcells were cultured in a well so that they adsorbed to thesurface of the well MNPs-Abs were then applied to the cell-cultured well followed by adding TMB and H

2O2to induce

a colorimetric reactionThis assay system displayed excellentspecificity sensitivity and linearity for quantitative detectionof the target molecules as well as the production of a colorsignal that could be detected by the naked eye

Based on the above system a nanocomposite-basedimmunoassay was also performed in which nanocompositeentrappingMNPs and Pt NPs in ordered mesoporous carbon(OMC) were utilized instead of HRP [33]This immunoassaygenerated significantly higher absorption intensity of colorsignal than the current ELISA and was able to quantify the

target antigen very rapidly within three minutes while theconventional ELISA requires several tens of minutes for colorsignal development [67 68] It showed a limit of detection(LOD) for HER2 of 15 ngmLminus1 in the linear range from 25 to100 ngmLminus1 The nanocomposite was found to have 50 timeshigher catalytic efficiency than that of free MNPs owing tothe high catalytic action of Pt NPs

Graphene oxide (GO) has been used in immunoassay as aperoxidase-mimicking nanozyme [41] Yanrsquos group developeda sandwich-type immunoassay for the detection of cancerbiomarker prostate specific antigen (PSA) In this work amagnetic bead (MB) was used to immobilize the primaryPSA antibody (Ab

1) and then a GO-conjugated secondary

antibody (Ab2) was applied in the presence of PSA Subse-

quentlyMB-Ab1was separated from the immunocomplex by

an external magnetic field and GO catalyzed the oxidation ofhydroquinone in the presence of H

2O2to generate a brown-

colored productConjugating both MNPs and Pt NPs on the surface of

GO enabled highly sensitive and rapid colorimetric detectionof the target cancer cell [35] In this work it was notablethat the electron transfer between MNPs and Pt NPs createsa synergistic effect significantly enhancing the catalyticperformance of MNPs-Pt NPs-GO nanohybrids Using thisimmunoassay system human breast adenocarcinoma cells(SKBR-3) which overexpressed HER2 were detected in fiveminutes with high specificity and sensitivity The LOD fortarget SKBR-3 cells was found to be about 100 cells in thelinear range from 100 to 1000 cells Moreover fluorescenceimaging of SKBR-3 was successfully performed with MNPs-Pt NPs-GO nanohybrids

322 Other Immunoassays By employing the superparam-agnetic property of MNPs a capture-detection immunoassaysystem has been developed by Gaorsquos group [63] In the proce-dure the CS-MNPs were conjugated with carcinoembryonicantibodies (anti-CEA M111147) and then mixed with thesample containing CEA After the CEA was captured byMNPs a magnetic field was applied to separate the MNPswhich had captured CEA Finally the MNPs capturing CEAwere injected into microplate wells coated with anothermonoclonal CEA antibody creating the sandwich formatThereby the MNPs prompted the generation of a color signalupon addition of colorimetric substrate and H

2O2to the

wells Cardiac troponin I (TnI) in serum a well-knownbiomarker for myocardial infarction was also detected by acapture-detection immunoassay utilizing the magnetism andperoxidase ability of MNPs [9]

33 Cancer Diagnostics without Immune Reaction Asidefrom immunoassay using antigen-antibody interaction othernovel assays using nanozymes have been developed partic-ularly for the diagnosis of tumor cells Asati and coworkersreported an assay for the determination of tumor cellswith poly(acrylic acid)-coated CeO

2NPs (nanoceria) as an

oxidase mimic [13] When the nanoparticles were conjugatedwith folic acid they bound to folate receptors on the tumorcell (A-549 lung cancer cells) due to high expression offolate receptors on the tumor cell surface Polymer-coated

6 Journal of Nanomaterials

nanoceria as an oxidase mimic made detection of tumorcells easier than with traditional immunoassay because itdirectly oxidized a colorimetric substrate to a colored productwithout H

2O2and additional steps to introduce an enzyme-

conjugated secondary antibody Further advances in thistechnology were also reported by employing a fluorescence-generating substrate ampliflu to detect target cancer cells ataround neutral pH [69]

Another interesting study to visualize target tumor tissueswithout the use of any additional targeting ligands hasalso been described [70] In this study peroxidase-like ironoxide nanoparticles were encapsulated inside a recombinanthuman heavy-chain ferritin (Hfn) protein shell which bindsto tumor cells that overexpress transferrin receptor 1The ironoxide cores catalyzed the oxidation of peroxidase substratesin the presence of H

2O2to produce the colorimetric signal

that was used to visualize tumor tissues Through thisstrategy nine types of cancer were successfully verified withenough specificity and sensitivity

34 Therapeutic Applications As described above nano-zymes have been widely used for detection and diagnos-tic methods Besides these applications many researchershave also studied therapeutic applications including anti-inflammatory effects neuroprotection stem cell growth andantiaging In general SOD was often utilized for therapeuticapplications owing to its protective role as a scavenger of reac-tive oxygen intermediates (ROIs) Intracellular concentrationof ROI including hydrogen peroxidase hypochlorite ionshydroxyl radicals hydroxyl ions and superoxide anions hasbeen known to be a cause of cell degeneration and associateddiseases [71] Inspired by earlier studies by Seal et al whichrevealed the activity of CeO

2NPs as a SOD-mimic [72 73]

various studies have been attempted to develop SOD-mimicking nanozymes

Chen at al reported that nanoceria as a SOD-mimicprevented retinal degeneration by inhibiting the productionof ROIs [74] In their work nanoceria prevented ROI-induced apoptosis and intracellular accumulation of ROIin cultured retinal neurons in the presence of H

2O2 They

further demonstrated that nanoceria injected into the eyes ofrats protected retina photoreceptor cells from light-induceddegeneration The study by Hirst et al also demonstratedthat nanoceria could be used for anti-inflammation byelimination of the radical oxygen species in J774A1 murinemacrophage cells [75]

Superparamagnetic iron oxide (SPIO) nanoparticles havebeen employed to promote growth of stem cells Huanget al reported that Ferucarbotran a commercialized SPIOcould promote cell growth in humanmesenchymal stem cells(hMSCs) by diminishing intracellular H

2O2and also accel-

erate cell cycle progression [76] In this report the intrinsicperoxidase-like activity of SPIO dramatically reduced intra-cellular H

2O2after internalization into hMSCs as well as

free iron ions released from lysosomal degradation of SPIO-affected cell cycle control molecules

35 Environmental Engineering Recently environmentalproblems such as water and air pollution food safety and

public health have become growing concerns in societyIn addition to the aforementioned applications nanozyme-based techniques have been explored for use in the field ofenvironmental technology

351 Pollutant Detection Ding et al developed a simpleand rapid colorimetric method for detecting melamine anorganic nitrogenous compound which is toxic when swal-lowed and has been illegally added to dairy products [77]The principle of this method is as follows Melamine inhibitsthe catalytic oxidation of colorimetric substrates (ABTS) byMNPs in the presence of H

2O2 because it competitively

reacts with H2O2 forming an additional compound Conse-

quently the intensity of the ABTS color signal was dependenton the concentration of melamine On the basis of thisreaction a colorimetric systemusingMNPs could enable easydetection by the naked eye of concentrations of melamineabove safety limits in dairy products

Nanocomposite-entrapping MNPs and oxidase in meso-porous carbonwere used to detect several phenol compoundsamperometrically such as phenol cresol and cathechol[49] These phenol compounds produced a concentration-dependent increase of cathodic current in this system whichmay have great potential in the field of environmentalmonitoring

352 Pollutant Removal Although there have been manymethods for removal of industrial dyestuffs such as absorp-tion precipitation and ultrasonic decomposition they couldnot efficiently degrade organic pollutants in wastewaterNanozyme-based methods have been found to be a power-ful cost-effective and simple method for degradation andmineralization of organic dyes from industrial processesMost prominently MNPs such as peroxidase have beeninvestigated for degradation of organic pollutants such asmethylene blue phenol and rhodamine B A MNP-baseddegradation method offers distinct advantages over existingdegradation methods which use HRP such as lower costhigh stability and reusability MNPs-H

2O2could remove

85 of phenol from aqueous solution within three hours[78] The MNPs-based degradation showed higher efficiencycompared to HRP-based degradation and stability in a broadrange of temperatures (5ndash90∘C) leading to ease of storageFurthermore MNPs could be captured by the application ofan external field and recycled for five rounds retaining almost100 of their activity Removal of methylene blue by MNPs-H2O2coupled method has also been successfully performed

by Jiang et al [79] It was observed that 96ofmethylene bluewas degraded in 15 minutes at optimized condition

Gao et al reported that MNPs-H2O2system could

degrade biofilm and kill resident bacteria [80] Biofilm espe-cially formed by Pseudomonas aeruginosa occurs in hospitalwater systems and medical devices with high frequencybecoming a common cause of nosocomial infection [81]In this report MNPs-H

2O2system exhibited significantly

higher efficiency than the use of H2O2in degradation of

biofilm The authors confirmed that additional free hydroxylradicals generated by MNP catalysis of H

2O2facilitated

the oxidative cleavage of biofilm components (nucleic acids

Journal of Nanomaterials 7

Table1Va

rious

applicationstu

dies

basedon

nano

zymes

Applicationfield

Nanozym

esAc

tivity

Detectio

nmetho

dDetails

Ref

Biosensor

MNPs

Peroxidase

Colorim

etric

H2O2biosensor

[9]

AuNPs

Glucose

oxidase

Colorim

etric

Nucleicacid

detection

[15]

Carboxyl-m

odified

graphene

oxide

Peroxidase

Colorim

etric

H2O2andglucoseb

iosensor

[23]

MNPs

Peroxidase

Colorim

etric

H2O2andglucoseb

iosensor

[44]

MNPs

Peroxidase

Colorim

etric

H2O2biosensor

[45]

MNPs

Peroxidase

Colorim

etric

H2O2biosensor

[46]

AuNPs

Peroxidase

Colorim

etric

H2O2andglucoseb

iosensor

[47]

MNPs

Peroxidase

Electro

chem

ical

Glucose

biosensor

[48]

MNPs

(with

oxidaseinmesop

orou

scarbo

n)Peroxidase

Electro

chem

ical

Glucose

biosensor

[49]

MNPs

(with

oxidaseinmesop

orou

ssilica)

Peroxidase

Colorim

etric

Glucose

andcholesterolbiosensor

[50]

MNPs

(with

oxidaseinmesop

orou

ssilica)

Peroxidase

Colorim

etric

Galactose

biosensor

[51]

MNPs

(with

oxidaseinmesop

orou

ssilica)

Peroxidase

Colorim

etric

Alcoh

olbiosensor

[52]

MNPs

Peroxidase

Colorim

etric

Nucleicacid

detection(Chlam

ydiatra

chom

atis)

[53]

CeO2NPs

Oxidase

Colorim

etric

Nucleicacid

detection(Chlam

ydiatra

chom

atis)

[56]

Chito

san-mod

ified

MNPs

with

thrombinaptamers

Peroxidase

Colorim

etric

Thrombindetection

[57]

Immun

oassay

MNPs

Peroxidase

Colorim

etric

Cardiactropo

ninI(Tn

I)detection

[9]

MNPs-PtN

Psin

mesop

orou

scarbo

nPeroxidase

Colorim

etric

Rotavirusa

ndHER

2detection

[33]

Graph

eneo

xide

Peroxidase

Colorim

etric

Prostatespecifica

ntigen

(PSA

)detectio

n[41]

Chito

san-mod

ified

MNPs

Peroxidase

Colorim

etric

Mou

seIgGandcarcinoembryonica

ntigen

detection

[63]

Prussia

nblue

mod

ified120574-Fe 2O3NPs

Peroxidase

Colorim

etric

IgGdetection

[64]

Ferritins

Peroxidase

Fluo

rometric

Avidin

andhu

man

ceruloplasmin

detection

[65]

MNPs

Peroxidase

Colorim

etric

Rotavirusa

ndHER

2detection

[66]

MNPs-PtN

Pson

graphene

oxide

Peroxidase

Colorim

etric

fluo

rometric

HER

2detectionandim

aging

[35]

Cancer

diagno

stics

(with

outimmun

ereactio

n)andtherapy

Poly(acrylicacid)-coated

CeO2NPs

Oxidase

Colorim

etric

Lung

cancer

celldetection

[13]

Poly(acrylicacid)-coated

CeO2NPs

Oxidase

Colorim

etric

Lung

andbreastcancer

celldetection

[69]

MagnetoferritinNPs

Peroxidase

Colorim

etric

fluo

rometric

Cancer

cellim

aging

[70]

CeO2NPs

Superoxide

dism

utase

Preventio

nof

retin

aldegeneratio

n[74]

CeO2NPs

Superoxide

dism

utase

Anti-infl

ammation

[75]

Superparam

agnetic

ironoxideN

PsPeroxidase

Prom

otionof

stem

cellgrow

th[76]

Environm

ental

engineering

MNPs

(with

oxidaseinmesop

orou

scarbo

n)Peroxidase

Electro

chem

ical

Phenolcresolandcathecho

ldetectio

n[49]

MNPs

Peroxidase

Colorim

etric

Mela

mined

etectio

n[77]

MNPs

Peroxidase

Removalof

phenol

[78]

MNPs

Peroxidase

Removalof

methylene

blue

[79]

MNPs

Peroxidase

Biofi

lmdegradation

[80]

8 Journal of Nanomaterials

proteins and polysaccharides) as well as killing residentbacteria

4 Conclusions and Future Research Aspects

Nanozymes have recently emerged as a potent alternativeto natural enzymes As discussed above although they arestill in the initial stages of research their use has developedsubstantially inmanydifferent detection and treatmentmeth-ods for biomolecules (Table 1) Despite the advantages ofnanozymes such as their low cost high stability robustnessease of mass production and long-term storability thereare several challenges to be tackled for practical use Firstlymost nanozymes have low activity compared to naturalenzymes Even if the nanomaterial itself is highly activeadditional coating and surface modification can decrease itsperformance Therefore development of novel nanozymesexhibiting high activity and appropriate surface-modificationtechniques are the emerging issues in the field of nanozymesNanozymes also have low selectivity to targets owing to theabsence of active sites where a substrate molecule binds andundergoes a chemical reaction in a natural enzyme Althoughresearchers have designed various types of surface-modifiednanozymes with polymers nucleic acids and antibodiesto provide selectivity mimicking natural enzymes this isstill insufficient for use in practical applications Toxicity ofnanozymes to humans and the ecosystem is also an essentialissue to be solved in regard to environmental and therapeuticapplications

In order for nanozymes to be positioned as a novelsource technology by efficiently overcoming the limitationsof natural enzymes we offer the following suggestions Thedevelopment of new nanozymes with higher activity andother positive properties than existing nanozymes is requiredWhile traditional research on developing nanozymes hasbeen performed by random screening of the enzyme-like activities of existing unspecified nanomaterials futureresearch will follow a strategy of rational screening ofenzyme-like activity based on those atomic compositionswhich are envisaged to catalyze enzymatic reactions Fur-thermore a strategy to prepare composites can be expectedto resolve the current major limitations of nanozymes oflow catalytic activity by exploiting their synergistic effectto facilitate electron transfer between composite materialsduring redox reaction Bioinspired synthesis of nanozymesalso provides an option to prepare nontoxic nanozymesby effectively circumventing the use of toxic chemicals inconventional chemical synthesis thereby accelerating theiruse in therapeutic applications Finally the developmentof novel surface engineering technology that can makenanozymes selective to target substrates will be importantin this field With the abovementioned research projects weexpect nanozymes to be widely employed in a wide range ofapplications in the near future

Conflict of Interests

The authors declare no financial or commercial conflict ofinterests

Acknowledgments

This work was supported by the Basic Science ResearchProgram through theNational Research Foundation of Korea(NRF) funded by the Ministry of Science ICT amp FuturePlanning (NRF-2014R1A1A1006016) and by the Gachon Uni-versity research fund of 2014 (GCU-2014-0110)

References

[1] D L Nelson and M M Cox Lehninger Principles of Biochem-istry vol 6 chapter 6 W H Freeman New York NY USA2005

[2] Z Liu R Cai L Mao H Huang and W Ma ldquoHighly sensitivespectrofluorimetric determination of hydrogen peroxide with120573-cyclodextrin-hemin as catalystrdquo Analyst vol 124 no 2 pp173ndash176 1999

[3] R P Bonar-Law and J K M Sanders ldquoPolyol recognition bya steroid-capped porphyrin Enhancement and modulation ofmisfit guest binding by added water or methanolrdquo Journal of theAmerican Chemical Society vol 117 no 1 pp 259ndash271 1995

[4] X-M Huang M Zhu L-Y Mao and H-X Shen ldquoCat-alytic determination of hydrogen peroxide by using themolybdenum-porphyrin complex as a mimetic enzyme ofperoxidaserdquo Analytical Sciences vol 13 no 1 pp 145ndash147 1997

[5] L Fruk andCMNiemeyer ldquoCovalent hemin-DNAadducts forgenerating a novel class of artificial heme enzymesrdquoAngewandteChemiemdashInternational Edition vol 44 no 17 pp 2603ndash26062005

[6] Q Wang Z Yang X Zhang X Xiao C K Chang and B XuldquoA supramolecular-hydrogel-encapsulated hemin as an artifi-cial enzyme to mimic peroxidaserdquo Angewandte Chemie Inter-national Edition vol 46 no 23 pp 4285ndash4289 2007

[7] Z Genfa and P K Dasgupta ldquoHematin as a peroxidase sub-stitute in hydrogen peroxide determinationsrdquo Analytical Chem-istry vol 64 no 5 pp 517ndash522 1992

[8] H Wei and E Wang ldquoNanomaterials with enzyme-like char-acteristics (nanozymes) next-generation artificial enzymesrdquoChemical Society Reviews vol 42 no 14 pp 6060ndash6093 2013

[9] L Gao J Zhuang LNie et al ldquoIntrinsic peroxidase-like activityof ferromagnetic nanoparticlesrdquo Nature Nanotechnology vol 2no 9 pp 577ndash583 2007

[10] R Polsky R Gill L Kaganovsky and I Willner ldquoNucleic acid-functionalized Pt nanoparticles catalytic labels for the ampli-fied electrochemical detection of biomoleculesrdquo AnalyticalChemistry vol 78 no 7 pp 2268ndash2271 2006

[11] T Li Y Du and E Wang ldquoPolyethyleneimine-functionalizedplatinum nanoparticles with high electrochemiluminescenceactivity and their applications to amplified analysis of bio-moleculesrdquo ChemistrymdashAn Asian Journal vol 3 no 11 pp1942ndash1948 2008

[12] W W He Y Liu J S Yuan et al ldquoAuPt nanostructures asoxidase and peroxidase mimetics for use in immunoassaysrdquoBiomaterials vol 32 no 4 pp 1139ndash1147 2011

[13] A Asati S Santra C Kaittanis S Nath and J M PerezldquoOxidase-like activity of polymer-coated cerium oxide nano-partielesrdquo Angewandte ChemiemdashInternational Edition vol 48no 13 pp 2308ndash2312 2009

[14] W J Luo C F Zhu S Su et al ldquoSelf-catalyzed self-limitinggrowth of glucose oxidase-mimicking gold nanoparticlesrdquo ACSNano vol 4 no 12 pp 7451ndash7458 2010

Journal of Nanomaterials 9

[15] X Zheng Q Liu C Jing et al ldquoCatalytic gold nanoparticles fornanoplasmonic detection of DNA hybridizationrdquo AngewandteChemie International Edition vol 50 no 50 pp 11994ndash119982011

[16] Y J Long Y F Li Y Liu J J Zheng J Tang and C JHuang ldquoVisual observation of the mercury-stimulated peroxi-dase mimetic activity of gold nanoparticlesrdquo Chemical Commu-nications vol 47 no 43 pp 11939ndash11941 2011

[17] W Chen J Chen Y-B Feng et al ldquoPeroxidase-like activityof water-soluble cupric oxide nanoparticles and its analyticalapplication for detection of hydrogen peroxide and glucoserdquoAnalyst vol 137 no 7 pp 1706ndash1712 2012

[18] W Luo Y-S Li J Yuan et al ldquoUltrasensitive fluorometricdetermination of hydrogen peroxide and glucose by usingmultiferroic BiFeO

3nanoparticles as a catalystrdquo Talanta vol 81

no 3 pp 901ndash907 2010[19] S H He W B Shi X D Zhang J A Li and Y M Huang ldquo120573-

Cyclodextrins-based inclusion complexes of CoFe2O4magnetic

nanoparticles as catalyst for the luminol chemiluminescencesystem and their applications in hydrogen peroxide detectionrdquoTalanta vol 82 no 1 pp 377ndash383 2010

[20] W B Shi X D Zhang S H He and Y M Huang ldquoCoFe2O4

magnetic nanoparticles as a peroxidasemimicmediated chemi-luminescence for hydrogen peroxide and glucoserdquo ChemicalCommunications vol 47 no 38 pp 10785ndash10787 2011

[21] Y W Fan and Y M Huang ldquoThe effective peroxidase-likeactivity of chitosan-functionalized CoFe

2O4nanoparticles for

chemiluminescence sensing of hydrogen peroxide and glucoserdquoAnalyst vol 137 no 5 pp 1225ndash1231 2012

[22] A K Dutta S K Maji D N Srivastava et al ldquoSynthesis ofFeS and FeSe nanoparticles from a single source precursor astudy of their photocatalytic activity peroxidase-like behaviorand electrochemical sensing of H

2O2rdquo ACS Applied Materials

and Interfaces vol 4 no 4 pp 1919ndash1927 2012[23] Y Song K Qu C Zhao J Ren and X Qu ldquoGraphene oxide

intrinsic peroxidase catalytic activity and its application toglucose detectionrdquoAdvancedMaterials vol 22 no 19 pp 2206ndash2210 2010

[24] Y Song X Wang C Zhao K Qu J Ren and X Qu ldquoLabel-free colorimetric detection of single nucleotide polymorphismby using single-walled carbon nanotube intrinsic peroxidase-like activityrdquo ChemistrymdashA European Journal vol 16 no 12 pp3617ndash3621 2010

[25] Y Guo J Li and S Dong ldquoHemin functionalized graphenenanosheets-based dual biosensor platforms for hydrogen per-oxide and glucoserdquo Sensors and Actuators B Chemical vol 160no 1 pp 295ndash300 2011

[26] J Xie X Zhang H Wang H Zheng Y Huang and J XieldquoAnalytical and environmental applications of nanoparticles asenzyme mimeticsrdquo TrACmdashTrends in Analytical Chemistry vol39 pp 114ndash129 2012

[27] A K Gupta and M Gupta ldquoSynthesis and surface engineeringof iron oxide nanoparticles for biomedical applicationsrdquoBioma-terials vol 26 no 18 pp 3995ndash4021 2005

[28] J Mu Y Wang M Zhao and L Zhang ldquoIntrinsic peroxidase-like activity and catalase-like activity of Co

3O4nanoparticlesrdquo

Chemical Communications vol 48 no 19 pp 2540ndash2542 2012[29] Y Wan P Qi D Zhang J Wu and Y Wang ldquoMan-

ganese oxide nanowire-mediated enzyme-linked immunosor-bent assayrdquo Biosensors and Bioelectronics vol 33 no 1 pp 69ndash74 2012

[30] R Andre F Natalio M Humanes et al ldquoV2O5nanowires

with an intrinsic peroxidase-like activityrdquo Advanced FunctionalMaterials vol 21 no 3 pp 501ndash509 2011

[31] W Chen J Chen A-L Liu L-M Wang G-W Li and X-H Lin ldquoPeroxidase-like activity of cupric oxide nanoparticlerdquoChemCatChem vol 3 no 7 pp 1151ndash1154 2011

[32] Y-L DongH-G Zhang Z U Rahman et al ldquoGraphene oxide-Fe3O4magnetic nanocomposites with peroxidase-like activity

for colorimetric detection of glucoserdquo Nanoscale vol 4 no 13pp 3969ndash3976 2012

[33] M I Kim Y Ye M-A Woo J Lee and H G Park ldquoA highlyefficient colorimetric immunoassay using a nanocompositeentrapping magnetic and platinum nanoparticles in orderedmesoporous carbonrdquo Advanced Healthcare Materials vol 3 no1 pp 36ndash41 2014

[34] J Liu X Hu S Hou et al ldquoAuPt coreshell nanorods withperoxidase- and ascorbate oxidase-like activities for improveddetection of glucoserdquo Sensors and Actuators B Chemical vol166-167 pp 708ndash714 2012

[35] M I Kim M S Kim M-AWoo et al ldquoHighly efficient colori-metric detection of target cancer cells utilizing superior catalyticactivity of graphene oxide-magnetic-platinum nanohybridsrdquoNanoscale vol 6 no 3 pp 1529ndash1536 2014

[36] M Liu H Zhao S Chen H Yu and X Quan ldquoInterface engi-neering catalytic graphene for smart colorimetric biosensingrdquoACS Nano vol 6 no 4 pp 3142ndash3151 2012

[37] Y Ye T Kong X Yu YWu K Zhang and XWang ldquoEnhancednonenzymatic hydrogen peroxide sensing with reducedgraphene oxideferroferric oxide nanocompositesrdquo Talantavol 89 pp 417ndash421 2012

[38] R Cui Z Han and J-J Zhu ldquoHelical carbon nanotubesintrinsic peroxidase catalytic activity and its application forbiocatalysis and biosensingrdquo ChemistrymdashA European Journalvol 17 no 34 pp 9377ndash9384 2011

[39] M Liu H Zhao S Chen H Yu and X Quan ldquoStimuli-responsive peroxidase mimicking at a smart graphene inter-facerdquo Chemical Communications vol 48 no 56 pp 7055ndash70572012

[40] S Liu J Tian L Wang Y Luo and X Sun ldquoA general strategyfor the production of photoluminescent carbon nitride dotsfrom organic amines and their application as novel peroxidase-like catalysts for colorimetric detection of H

2O2and glucoserdquo

RSC Advances vol 2 no 2 pp 411ndash413 2012[41] F Qu T Li and M Yang ldquoColorimetric platform for visual

detection of cancer biomarker based on intrinsic peroxidaseactivity of graphene oxiderdquo Biosensors and Bioelectronics vol26 no 9 pp 3927ndash3931 2011

[42] W Shi QWang Y Long et al ldquoCarbon nanodots as peroxidasemimetics and their applications to glucose detectionrdquo ChemicalCommunications vol 47 no 23 pp 6695ndash6697 2011

[43] X Wang K Qu B Xu J Ren and X Qu ldquoMulticolorluminescent carbon nanoparticles synthesis supramolecularassembly with porphyrin intrinsic peroxidase-like catalyticactivity and applicationsrdquo Nano Research vol 4 no 9 pp 908ndash920 2011

[44] H Wei and E Wang ldquoFe3O4magnetic nanoparticles as per-

oxidase mimetics and their applications in H2O2and glucose

detectionrdquo Analytical Chemistry vol 80 no 6 pp 2250ndash22542008

[45] Q Chang KDeng L ZhuG Jiang C Yu andH Tang ldquoDeter-mination of hydrogen peroxide with the aid of peroxidase-like

10 Journal of Nanomaterials

Fe3O4magnetic nanoparticles as the catalystrdquo Microchimica

Acta vol 165 no 3-4 pp 299ndash305 2009[46] Z Jiang L Kun H Ouyang A Liang and H Jiang ldquoA simple

and sensitive fluorescence quenching method for the determi-nation of H

2O2using rhodamine B and Fe

3O4nanocatalystrdquo

Journal of Fluorescence vol 21 no 5 pp 2015ndash2020 2011[47] Y Jv B Li andR Cao ldquoPositively-charged gold nanoparticles as

peroxidiase mimic and their application in hydrogen peroxideand glucose detectionrdquo Chemical Communications vol 46 no42 pp 8017ndash8019 2010

[48] K Wang J-J Xu D-C Sun H Wei and X-H Xia ldquoSelectiveglucose detection based on the concept of electrochemicaldepletion of electroactive species in diffusion layerrdquo Biosensorsand Bioelectronics vol 20 no 7 pp 1366ndash1372 2005

[49] M I Kim Y Ye B Y Won S Shin J Lee and H G Park ldquoAhighly efficient electrochemical biosensing platform by employ-ing conductive nanocomposite entrapping magnetic nano-particles and oxidase in mesoporous carbon foamrdquo AdvancedFunctional Materials vol 21 no 15 pp 2868ndash2875 2011

[50] M I Kim J Shim T Li J Lee and H G Park ldquoFabrica-tion of nanoporous nanocomposites entrapping Fe

3O4mag-

netic nanoparticles and oxidases for colorimetric biosensingrdquoChemistrymdashAEuropean Journal vol 17 no 38 pp 10700ndash107072011

[51] M I Kim J Shim T Li et al ldquoColorimetric quantificationof galactose using a nanostructured multi-catalyst systementrapping galactose oxidase and magnetic nanoparticles asperoxidasemimeticsrdquoAnalyst vol 137 no 5 pp 1137ndash1143 2012

[52] M I Kim J Shim H J Parab S C Shin J Lee and H G ParkldquoA convenient alcohol sensor using one-pot nanocompositeentrapping alcohol oxidase and magnetic nanoparticles as per-oxidase mimeticsrdquo Journal of Nanoscience and Nanotechnologyvol 12 no 7 pp 5914ndash5919 2012

[53] K S Park M I Kim D-Y Cho and H G Park ldquoLabel-free colorimetric detection of nucleic acids based on target-induced shielding against the peroxidase-mimicking activity ofmagnetic nanoparticlesrdquo Small vol 7 no 11 pp 1521ndash1525 2011

[54] J A Brinkman M Z Rahmani W E Jones A K Chaturvediand M E Hagensee ldquoOptimization of PCR based detection ofhuman papillomavirus DNA from urine specimensrdquo Journal ofClinical Virology vol 29 no 4 pp 230ndash240 2004

[55] L Hafner K Beagley and P Timms ldquoChlamydia trachomatisinfection host immune responses and potential vaccinesrdquoMucosal Immunology vol 1 no 2 pp 116ndash130 2008

[56] M I Kim K S Park and H G Park ldquoUltrafast colorimetricdetection of nucleic acids based on the inhibition of the oxidaseactivity of cerium oxide nanoparticlesrdquo Chemical Communica-tions vol 50 no 67 pp 9577ndash9580 2014

[57] Z Zhang Z Wang X Wang and X Yang ldquoMagneticnanoparticle-linked colorimetric aptasensor for the detection ofthrombinrdquo Sensors and Actuators B Chemical vol 147 no 2 pp428ndash433 2010

[58] B W Blais and A Martinez-Perez ldquoDetection of groupD salmonellae including Salmonella enteritidis in eggs bypolymyxin-based enzyme-linked immunosorbent assayrdquo Jour-nal of Food Protection vol 71 no 2 pp 392ndash396 2008

[59] V Tripathi S Nara S K Chaube et al ldquoDevelopment ofrapid and sensitive one-step direct enzyme linked immunosor-bent assay for 17-120572-OH-progesterone in serumrdquo Journal ofImmunoassay and Immunochemistry vol 29 no 2 pp 117ndash1272008

[60] K DMcReynolds M J Hadd and J Gervay-Hague ldquoSynthesisof biotinylated glycoconjugates and their use in a novel ELISAfor direct comparison ofHIV-1 gp120 recognition ofGalCer andrelated carbohydrate analoguesrdquo Bioconjugate Chemistry vol10 no 6 pp 1021ndash1031 1999

[61] H Hocini S Iscaki J-P Bouvet M D Kazatchkine and LBelec ldquoAn ELISA method to measure total and specific humansecretory IgA subclasses based on selective degradation by IgA1-proteaserdquo Journal of Immunological Methods vol 235 no 1-2pp 53ndash60 2000

[62] L Micheli S Di Stefano D Moscone et al ldquoProduction ofantibodies and development of highly sensitive formats ofenzyme immunoassay for saxitoxin analysisrdquo Analytical andBioanalytical Chemistry vol 373 no 8 pp 678ndash684 2002

[63] L Gao J Wu S Lyle K Zehr L Cao and D Gao ldquoMagnetitenanoparticle-linked immunosorbent assayrdquo Journal of PhysicalChemistry C vol 112 no 44 pp 17357ndash17361 2008

[64] X-Q Zhang S-W Gong Y Zhang T Yang C-YWang andNGu ldquoPrussian blue modified iron oxide magnetic nanoparticlesand their high peroxidase-like activityrdquo Journal of MaterialsChemistry vol 20 no 24 pp 5110ndash5116 2010

[65] Z Tang H Wu Y Zhang Z Li and Y Lin ldquoEnzyme-mimicactivity of ferric nano-core residing in ferritin and its biosensingapplicationsrdquo Analytical Chemistry vol 83 no 22 pp 8611ndash8616 2011

[66] M-A Woo M I Kim J H Jung K S Park T S Seoand H G Park ldquoA novel colorimetric immunoassay utilizingthe peroxidase mimicking activity of magnetic nanoparticlesrdquoInternational Journal of Molecular Sciences vol 14 no 5 pp9999ndash10014 2013

[67] V H C Bramwell G S Doig A B Tuck et al ldquoChangesover time of extracellular domain of HER2 (ECDHER2) serumlevels have prognostic value in metastatic breast cancerrdquo BreastCancer Research andTreatment vol 114 no 3 pp 503ndash511 2009

[68] K S Asgeirsson A Agrawal C Allen et al ldquoSerum epidermalgrowth factor receptor and HER2 expression in primary andmetastatic breast cancer patientsrdquo Breast Cancer Research vol9 no 6 article R75 2007

[69] A Asati C Kaittanis S Santra and J M Perez ldquoPH-tunableoxidase-like activity of cerium oxide nanoparticles achievingsensitive fluorigenic detection of cancer biomarkers at neutralpHrdquo Analytical Chemistry vol 83 no 7 pp 2547ndash2553 2011

[70] K L Fan C Q Cao Y X Pan et al ldquoMagnetoferritinnanoparticles for targeting and visualizing tumour tissuesrdquoNature Nanotechnology vol 7 no 7 pp 459ndash464 2012

[71] S Beatty H-H Koh M Phil D Henson and M BoultonldquoThe role of oxidative stress in the pathogenesis of age-relatedmacular degenerationrdquo Survey of Ophthalmology vol 45 no 2pp 115ndash134 2000

[72] C Korsvik S Patil S Seal and W T Self ldquoSuperoxidedismutase mimetic properties exhibited by vacancy engineeredceria nanoparticlesrdquo Chemical Communications no 10 pp1056ndash1058 2007

[73] E G Heckert A S Karakoti S Seal andW T Self ldquoThe role ofcerium redox state in the SOD mimetic activity of nanoceriardquoBiomaterials vol 29 no 18 pp 2705ndash2709 2008

[74] J Chen S Patil S Seal and J F McGinnis ldquoRare earthnanoparticles prevent retinal degeneration induced by intracel-lular peroxidesrdquo Nature Nanotechnology vol 1 no 2 pp 142ndash150 2006

Journal of Nanomaterials 11

[75] S M Hirst A S Karakoti R D Tyler N Sriranganathan SSeal and C M Reilly ldquoAnti-inflammatory properties of ceriumoxide nanoparticlesrdquo Small vol 5 no 24 pp 2848ndash2856 2009

[76] D-M Huang J-K Hsiao Y-C Chen et al ldquoThe promotion ofhuman mesenchymal stem cell proliferation by superparamag-netic iron oxide nanoparticlesrdquo Biomaterials vol 30 no 22 pp3645ndash3651 2009

[77] N Ding N Yan C Ren and X Chen ldquoColorimetric determi-nation of melamine in dairy products by Fe

3O4Magnetic nano-

particles-H2O2-ABTS detection systemrdquo Analytical Chemistry

vol 82 no 13 pp 5897ndash5899 2010[78] J Zhang J Zhuang L Gao et al ldquoDecomposing phenol by the

hidden talent of ferromagnetic nanoparticlesrdquo Chemospherevol 73 no 9 pp 1524ndash1528 2008

[79] J Z Jiang J Zou L H Zhu L Huang H Jiang and YZhang ldquoDegradation of methylene blue with H

2O2activated

by peroxidase-like Fe3O4magnetic nanoparticlesrdquo Journal of

Nanoscience and Nanotechnology vol 11 no 6 pp 4793ndash47992011

[80] L Gao K M Giglio J L Nelson H Sondermann and AJ Travis ldquoFerromagnetic nanoparticles with peroxidase-likeactivity enhance the cleavage of biological macromolecules forbiofilm eliminationrdquo Nanoscale vol 6 no 5 pp 2588ndash25932014

[81] K Vickery A Pajkos and Y Cossart ldquoRemoval of biofilmfrom endoscopes evaluation of detergent efficiencyrdquo AmericanJournal of Infection Control vol 32 no 3 pp 170ndash176 2004

Submit your manuscripts athttpwwwhindawicom

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CorrosionInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Polymer ScienceInternational Journal of

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materials

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal ofNanomaterials

Page 2: Review Article Recent Research Trends and Future …downloads.hindawi.com/journals/jnm/2015/756278.pdfnovel biosensor, immunoassay, cancer diagnostics, therapeutics, and environmental

2 Journal of Nanomaterials

NanozymesImmunoassay

Environmental engineering

Biosensor

Cancer diagnostics and therapy

Figure 1 Awide range of applications in the field of nanozymesThe images of nanomaterials in the center ring represent (clockwise from topleft) Fe

3O4nanoparticle CeO

2nanoparticle graphene oxide andAunanoparticle which are the typical nanomaterials exhibiting enzyme-like

activities

immunoassay cancer diagnostics therapeutics and environ-mental engineering We also provide challenges and researchtrends in the emerging nanozyme research field (Figure 1)

2 Fundamentals of Nanozymes

Due to the absence of an active site in nanozymes where onlya specific substrate molecule binds and undergoes a chem-ical reaction researchers have developed various strategiesto endow nanozymes with specificity to target moleculesThe most representative strategies can be divided betweenthe oxidase-coupled method and the surface-modificationmethod In the oxidase-coupled method nanozymes withperoxidase-like activity gain their specificity by being coupledwith oxidase which generatesH

2O2as a product of a catalytic

reaction which occurs only in the presence of the targetmolecule Peroxidase-like nanozymes subsequently catalyzethe oxidation of colorimetric substrates with the resultingH2O2 For the surface-modification method an antibody

is generally conjugated on the surface of the nanozyme toprovide specificity toward antigen molecules mostly in thecolorimetric immunoassay system By conjugation of theantibody specific to the target antigen on the surface ofthe nanozyme the nanozyme can act as a target-specificprobe generating a colorimetric signal in the presence of thecolorimetric substrate andH

2O2 In the samemanner ligand-

conjugated nanozymes can specifically bind to target recep-tors and produce a colorimetric signal when the targetedmolecules bind on the nanozymesrsquo surface Aptamers areattracting interest in the fields of therapeutics and diagnostics

and are becoming promising candidates for use in givingspecificity to nanozyme-based biosensors

The intrinsic enzyme-like activities of nanozymes aregenerally believed to be produced by atoms present on thesurface as well as in the nanozymersquos inside core Thus theatomic composition of nanozymes is the most importantfactor in determining their catalytic activity although otherfactors such as size morphology surface coating and mod-ification pH and temperature can also have an impact[8] Based on the type of composition nanozymes can bedistributed into three categories metal oxide-based metal-based and carbon-based nanozymes

21 Metal Oxide-Based Nanozymes Metal oxide nanopar-ticles have been widely used in the field of biomedicalapplications such as biosensor targeted drug delivery tis-sue repair immunoassay and contrast agents in magneticresonance imaging (MRI) and cell separation [27] Sincemetal oxide nanoparticles are commonly considered chem-ically and biologically inert additional surface engineeringand subsequent conjugation with functional substances arerequired to endowmetal oxide nanoparticles with functional-ity Recently inspired by the notable discovery of the intrinsiccatalytic activity of MNP as a peroxidase [9] metal oxide-type nanozymes have attracted great interest with a largenumber of papers discussing newly reported enzyme-likeactivities of these nanomaterials A variety of metal oxide-based nanozymes have been discovered to possess enzyme-like catalytic activities (peroxidase catalase and superoxidedismutase (SOD)) including MNPs [9] CeO

2NPs [13]

Journal of Nanomaterials 3

cobalt oxide nanoparticles (Co3O4NPs) [28] manganese

dioxide nanoparticles (MnO2NPs) [29] vanadiumpentoxide

nanoparticles (V2O5NPs) [30] and CuONPs [31] Generally

metal oxide-based nanozymes with peroxidase-like activityhave been those most widely investigated by researchersowing to their convenience for constructing amperometricand colorimetric detection systems by utilizing the capabilityof peroxidase to catalyze certain substrates which generatethe corresponding electric and colorimetric signal in thepresence of hydrogen peroxide (H

2O2) Herein we focus

on colorimetric detection systems utilizing peroxidase-likenanozymes and associated applications

22 Metal-Based Nanozymes Metal-based nanozymes suchas Au NPs and Pt NPs have been discovered to pos-sess the catalytic activities of oxidase peroxidase catalaseand SOD In addition to the single nanoparticle systemmentioned above nanocomposites which combine a metal-based nanozyme with other nanozymes have been alsointensively developed including Fe

3O4-graphene oxide (GO)

[32] Fe3O4-Pt [33] Au-Pt [34] and GO-Fe

3O4-Pt [35]

nanocomposites Surprisingly it was reported that metal-based nanozymes often exhibit synergistic effects whichsignificantly enhance catalytic performance when coupledwith other nanozymes as a composite [33]

23 Carbon-Based Nanozymes Carbon-based nanozymessuch as fullerene carbon nanotube graphene oxide andcarbon dot are also attracting great interest owing to theirunique enzyme-mimicking activities [23ndash25 36ndash43] Theyhave been found to possess peroxidase and SOD-mimickingabilities and are widely utilized as signaling agents forsignal amplification and detection of analytes in the field ofbiosensors and immunoassays

3 Recent Applications

31 Biosensors In recent time horseradish peroxidase(HRP) which can catalyze the oxidation of a variety ofsubstrates by H

2O2 has been one of the most commonly

used enzymes for the construction of biosensors In spiteof its high catalytic efficiency HRP-based biosensors havecritical problems in that the catalytic activity of HRP is proneto degradation in long-term storage and harsh conditionsthereby leading to errors in the process of sensing To solvethis problem a peroxidase-like nanozyme which is highlyrobust against environmental conditions is utilized in placeof HRP providing a cost-effective method of fabrication ofbiosensors

311 H2O2 Detection H2O2 detection plays an essential rolein the fields of biologymedicine environmental engineeringand food industry Since H

2O2 a product of an incompletely

reduced metabolite of oxygen is generated as a by-productof various biological pathways and is a contaminant inseveral industrial products and wastes H

2O2detection is of

practical importance in the field of biosensors With sub-stantial progress in biosensing technology various methodsfor H2O2detection have been reported Among them is the

colorimetric signal readout strategy based on a redox reac-tion between HRP and colorimetric substrates such as 221015840-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS)and 331015840551015840-tetramethylbenzidine (TMB) This strategy hasbeen actively developed due to its high sensitivity selectiv-ity and simplicity for detecting H

2O2 However since the

colorimetric detection method using HRP has problems oflow stability and high cost nanozymes showing peroxidase-like activity have been intensively utilized to resolve thesedrawbacks Beginning with the remarkable discovery thatMNPs exhibit intrinsic peroxidase-like activity [9] manyresearchers have focused on the development of novel H

2O2

detection methods employing various nanozymes Here wediscuss recent applications of various nanozymes in H

2O2

detectionAfter Yanrsquos report H

2O2detection methods with MNPs

(used as peroxidase-like nanozymes) were further developedby Wei and Wang [44] This research outlined a colorimetricdetection method for H

2O2 in which MNPs were used to

catalyze the oxidation of ABTS in the presence of H2O2

The catalytic oxidation of ABTS with H2O2generates green-

colored products by which H2O2can be detected by the

naked eyeThey noted that ABTS could be oxidized by H2O2

in the absence of any catalysts but demonstrated that thepresence ofMNPs gave a 320 higher response of absorptionspectra when compared with the absence of MNPs Not onlythe peroxidase-like catalytic activity of Fe

3O4MNPs but also

their high stability in rough conditions (pH and temperature)was confirmed with additional investigations

Based on the colorimetric detection method abovemany approaches have proceeded by varying the colori-metric substrates and nanozymes used NN-Dimethyl-p-phenylenediamine sulfate (DPD) was used as a colorimetricsubstrate in place of ABTS [45] The DPD-MNPs analyticalsystem showed several advantages (lower operating temper-ature and detection limit and higher sensitivity) over thesystem using ABTS because DPD is more easily oxidized byH2O2than ABTS and because oxidized DPD (DPD+) pro-

duces a colored product with a strong absorption maximumat 550 nm Aside from the signal-on colorimetric methodabove Jiangrsquos group has developed a new type of fluorescencemethod using rhodamine B (RhB) as a substrate [46] Inthis method MNPs catalyze H

2O2to form the radical OH

which can oxidize RhB to form colorless and nonfluorescentproducts In short the more the H

2O2exists the weaker the

fluorescence intensity of RhB isOther nanozymes have been also reported to detect

H2O2 Au NPs have been discovered to possess intrinsic

peroxidase-like activity [47] Caorsquos studies reported thatpositively charged Au NPs can catalyze the oxidation of TMBby H2O2 Carboxyl-modified graphene oxide was shown to

possess intrinsic peroxidase-like activity that can catalyze thereaction of TMB in the presence of H

2O2to produce a blue-

color reaction [23] Concentrations as low as 5 times 10minus8mol Lminus1H2O2were detected with a linear range from 5 times 10minus8 to 1 times

10minus6mol Lminus1

312 Glucose Detection Peroxidase-like nanozymes coupledwith glucose oxidase (GOx) have been frequently employed

4 Journal of Nanomaterials

in the construction of glucose biosensors Wang et al devel-oped a colorimetric glucose detection platform by combiningthe catalytic oxidation of glucose with GOx and the catalyticreaction of ABTS withMNPs [48] Glucose concentrations aslow as 30 120583M were detected with a linear range from 50 120583Mto 1mM in this study

There have been several reports of an electrochemi-cal biosensing platform using GOx-coupled nanozymes Ahighly efficient and robust electrochemical biosensing strat-egy employing a nanocomposite harboring GOx-couplednanozymes was developed by our group [49] In this reportMNPs and GOx were entrapped in the pores of mesoporouscarbon in which GOx immobilized in the nanocompositegenerates H

2O2which then is directly reduced to H

2O

with the electrocatalytic reduction mediated by MNPs Thissystem showed a linear range of (05 to 10) times 10minus3M and adetection limit of 02 times 10minus3M

313 Oxidase-Coupled Methods (Except Glucose Oxidase)On the basis of the mechanism of glucose detection aboveseveral different oxidases have also been coupled withnanozymes for the fabrication of biosensing platforms Ananostructured multicatalyst system consisting of MNPsand cholesterol oxidase entrapped in large-pore-sized meso-porous silica has been developed for convenient colorimetricdetection of cholesterol [50] This multicatalyst system iscomposed of MNPs incorporated in the wall of mesocellularsilica pores forming magnetic mesoporous silica (MMS)and cholesterol oxidases In this system cholesterol oxidaseimmobilized in the MMS promotes a reaction with choles-terol to generate H

2O2 which subsequently activates MNPs

in the mesocellular silica pores to convert a colorimetric sub-strate into a colored product The result of this investigationshows the cholesterol oxidase-coupled method to have highselectivity and sensitivity (limit of detection LOD of 5120583Min the linear range from 10 to 250 120583M) for the detection ofcholesterol A colorimetricmethod for detection of galactosewhich utilizes a nanostructured multicatalyst system consist-ing of MNPs and galactose oxidase has also been reported[51] The clinical applicability of this multicatalytic systemwas successfully evaluated as a promising analytical tool todiagnose galactosemia by determining the concentration ofgalactose eluted from the dried blood specimens provided byclinical hospitals

Apart from the above oxidases alcohol oxidase has beenused in a colorimetric biosensor for quantification of ethanoland methanol [52] The nanocomposite system utilizingalcohol oxidase entrapped in mesocellular silica with MNPsprovided a rapid and convenient platform for analysis ofalcohol with high stability and reusability It showed a linearconcentration range from 100 to 500120583M with a detectionlimit as low as 25 120583M

314 OtherMethods Recently peroxidase-mimicking nano-materials such as MNPs CeO

2NPs and Au NPs [15] have

been employed for new methods of DNA detection A label-free colorimetric detection method for nucleic acids hasbeen developed [53] In this method the target DNA inthe sample which is amplified by polymerase chain reaction

(PCR) is directly adsorbed on the surface of the MNPs dueto electrostatic interactions between the negatively chargedphosphate backbone and the positively charged surface of theNPs thereby inducing a shielding effect against colorimetricsubstrate binding to MNPs The peroxidase activity of MNPswill decrease due to the DNA-induced shielding so thatthe intensity of the color signal will also be significantlyreduced Using this detection method researchers succes-sively detectedChlamydia trachomatis in humanurine whichis one of the common bacteria causing sexually transmitteddisease (STD) [54 55] CeO

2NPs were also employed in a

label-free colorimetric method for detecting C trachomatisand this method provided ultrafast detection of the targetnucleic acid (target nucleic acids can be determined withina few minutes) [56]

A novel biosensing format using aptamers has been devel-oped by several researchers based on the fact that aptamerswhich are ssDNA or ssRNA that can specifically bind to atarget can replace antibodies for the specific recognition oftarget molecules A method using chitosan-modified MNPsconjugated with thrombin aptamers was reported by Zhangrsquosgroup [57] They constructed a sandwich-type assay for thedetection of thrombin with two thrombin aptamers Thisaptamer-based assay showed a linear detection range from 1to 100 nM and a detection limit of 1 nM of thrombin

32 Immunoassays Immunoassays have been used in hos-pitals laboratory medicine and research to improve thehealth and well-being of humans and animals Informationgained by clinical immunoassay testing has shortened thelength of hospital stays and decreased the severity of illnessby identifying and assessing the progression of diseasethereby leading to improved therapeutic choices In lifescience research immunoassays are used in the study ofbiological systems for tracking different proteins hormonesand antibodies In industry immunoassays are used to detectcontaminants in food and water and in quality control tomonitor specific molecules used during product processingHowever themost commonly used enzymes in immunoassayinclude horseradish peroxidase and alkaline phosphatase[58ndash62] which lose their enzymatic activities gradually overlong-term storage [63] To overcome these limits variousstudies on replacing natural enzymes have been reported andconsequently novel types of immunoassay using nanozymesin place of HRP have been developed

321 Sandwich or Antigen-Down Type Immunoassays Gaoand coworkers reported an immunoassay using chitosan-modified MNPs (CS-MNPs) as a replacement for HRP in thetraditional immunoassay [63] They provided protocols forantigen-down and sandwich immunoassays with CS-MNPsand detected mouse IgG and carcinoembryonic antigen(CEA) respectively Chitosan modified on the surface ofMNPs prevented aggregation of MNPs so that MNPs wereeasily dispersed in aqueous solutions Meanwhile aminogroups in the chitosan provided a convenient site for covalentlinking of antibodies to MNPs thereby replacing the linkageof HRP-conjugated antibodies to CS-MNP-conjugated anti-bodies in the immunoassay Capture-detection immunoassay

Journal of Nanomaterials 5

was also developed to detect CEA by employing themagneticproperties of CS-MNPs which facilitate capturing separat-ing and enriching antigens as well as redispersing the MNPaggregation in solution

Zhang and coworkers reported a novel immunoassayutilizing Prussian blue modified 120574-Fe

2O3NPs [64] Prus-

sian blue a dark blue pigment with the idealized formulaFe7(CN)18 was modified on the surface of 120574-Fe

2O3NPs due

to its excellent electrochemical behavior that accelerated elec-tron transfer and its catalytic properties that could catalyzethe reduction of H

2O2 Prussian blue modified 120574-Fe

2O3NPs

(PBMNPs) were next conjugated with staphylococcal proteinA (SPA) to bind to IgG immobilized in the well so thatPBMNPs could derive a colorimetric reaction in the presenceof TMB and H

2O2

Ferritins nanoscale globular protein cages encapsulatinga ferric core were used in immunoassay in Tang et alrsquos study[65] In this study ferritin showed a thermally stable and pH-tolerable enzyme-mimetic activity derived from the ferricnanocore of ferritin Two forms of immunoassay systemswere constructed antigen-down type and sandwich typeAvidin was selected as the target molecule of the antigen-down immunoassay and nitrated human ceruloplasmin asthe target molecule of the sandwich-type immunoassayTheyalso reported that the ferritins could be utilized in analyticalapplications such as H

2O2assay In their assay ferritin

oxidizes the p-HPPA in the presence of H2O2to generate

a fluorescent product This ferritin-based H2O2assay shows

a detection limit of 016 120583M and a linear detection range of40 120583M which is one-order higher sensitivity with a broaderlinear response range

Immunoassay systems for detection of rotavirus andbreast cancer have been developed [66] in which MNPsare conjugated to antibodies against rotaviruses and humanepidermal growth factor receptor 2 (HER2) In this sys-tem sandwich-type and antigen-down type immunoassaywere used to detect rotavirus and HER2 respectively Forthe detection of rotavirus rotavirus antibodies were firstimmobilized in a well and rotavirus bound to the immo-bilized antibody Subsequently MNP-conjugated antibodies(MNP-Abs) were added to the well in order to bind tocaptured rotaviruses Finally the peroxidase substrate TMBwas changed into blue-colored products in the presence ofH2O2 An antigen-down immunoassay system was used in

the case of breast cell detection which did not require priorimmobilization of antibodies in the bare well surface Breastcells were cultured in a well so that they adsorbed to thesurface of the well MNPs-Abs were then applied to the cell-cultured well followed by adding TMB and H

2O2to induce

a colorimetric reactionThis assay system displayed excellentspecificity sensitivity and linearity for quantitative detectionof the target molecules as well as the production of a colorsignal that could be detected by the naked eye

Based on the above system a nanocomposite-basedimmunoassay was also performed in which nanocompositeentrappingMNPs and Pt NPs in ordered mesoporous carbon(OMC) were utilized instead of HRP [33]This immunoassaygenerated significantly higher absorption intensity of colorsignal than the current ELISA and was able to quantify the

target antigen very rapidly within three minutes while theconventional ELISA requires several tens of minutes for colorsignal development [67 68] It showed a limit of detection(LOD) for HER2 of 15 ngmLminus1 in the linear range from 25 to100 ngmLminus1 The nanocomposite was found to have 50 timeshigher catalytic efficiency than that of free MNPs owing tothe high catalytic action of Pt NPs

Graphene oxide (GO) has been used in immunoassay as aperoxidase-mimicking nanozyme [41] Yanrsquos group developeda sandwich-type immunoassay for the detection of cancerbiomarker prostate specific antigen (PSA) In this work amagnetic bead (MB) was used to immobilize the primaryPSA antibody (Ab

1) and then a GO-conjugated secondary

antibody (Ab2) was applied in the presence of PSA Subse-

quentlyMB-Ab1was separated from the immunocomplex by

an external magnetic field and GO catalyzed the oxidation ofhydroquinone in the presence of H

2O2to generate a brown-

colored productConjugating both MNPs and Pt NPs on the surface of

GO enabled highly sensitive and rapid colorimetric detectionof the target cancer cell [35] In this work it was notablethat the electron transfer between MNPs and Pt NPs createsa synergistic effect significantly enhancing the catalyticperformance of MNPs-Pt NPs-GO nanohybrids Using thisimmunoassay system human breast adenocarcinoma cells(SKBR-3) which overexpressed HER2 were detected in fiveminutes with high specificity and sensitivity The LOD fortarget SKBR-3 cells was found to be about 100 cells in thelinear range from 100 to 1000 cells Moreover fluorescenceimaging of SKBR-3 was successfully performed with MNPs-Pt NPs-GO nanohybrids

322 Other Immunoassays By employing the superparam-agnetic property of MNPs a capture-detection immunoassaysystem has been developed by Gaorsquos group [63] In the proce-dure the CS-MNPs were conjugated with carcinoembryonicantibodies (anti-CEA M111147) and then mixed with thesample containing CEA After the CEA was captured byMNPs a magnetic field was applied to separate the MNPswhich had captured CEA Finally the MNPs capturing CEAwere injected into microplate wells coated with anothermonoclonal CEA antibody creating the sandwich formatThereby the MNPs prompted the generation of a color signalupon addition of colorimetric substrate and H

2O2to the

wells Cardiac troponin I (TnI) in serum a well-knownbiomarker for myocardial infarction was also detected by acapture-detection immunoassay utilizing the magnetism andperoxidase ability of MNPs [9]

33 Cancer Diagnostics without Immune Reaction Asidefrom immunoassay using antigen-antibody interaction othernovel assays using nanozymes have been developed partic-ularly for the diagnosis of tumor cells Asati and coworkersreported an assay for the determination of tumor cellswith poly(acrylic acid)-coated CeO

2NPs (nanoceria) as an

oxidase mimic [13] When the nanoparticles were conjugatedwith folic acid they bound to folate receptors on the tumorcell (A-549 lung cancer cells) due to high expression offolate receptors on the tumor cell surface Polymer-coated

6 Journal of Nanomaterials

nanoceria as an oxidase mimic made detection of tumorcells easier than with traditional immunoassay because itdirectly oxidized a colorimetric substrate to a colored productwithout H

2O2and additional steps to introduce an enzyme-

conjugated secondary antibody Further advances in thistechnology were also reported by employing a fluorescence-generating substrate ampliflu to detect target cancer cells ataround neutral pH [69]

Another interesting study to visualize target tumor tissueswithout the use of any additional targeting ligands hasalso been described [70] In this study peroxidase-like ironoxide nanoparticles were encapsulated inside a recombinanthuman heavy-chain ferritin (Hfn) protein shell which bindsto tumor cells that overexpress transferrin receptor 1The ironoxide cores catalyzed the oxidation of peroxidase substratesin the presence of H

2O2to produce the colorimetric signal

that was used to visualize tumor tissues Through thisstrategy nine types of cancer were successfully verified withenough specificity and sensitivity

34 Therapeutic Applications As described above nano-zymes have been widely used for detection and diagnos-tic methods Besides these applications many researchershave also studied therapeutic applications including anti-inflammatory effects neuroprotection stem cell growth andantiaging In general SOD was often utilized for therapeuticapplications owing to its protective role as a scavenger of reac-tive oxygen intermediates (ROIs) Intracellular concentrationof ROI including hydrogen peroxidase hypochlorite ionshydroxyl radicals hydroxyl ions and superoxide anions hasbeen known to be a cause of cell degeneration and associateddiseases [71] Inspired by earlier studies by Seal et al whichrevealed the activity of CeO

2NPs as a SOD-mimic [72 73]

various studies have been attempted to develop SOD-mimicking nanozymes

Chen at al reported that nanoceria as a SOD-mimicprevented retinal degeneration by inhibiting the productionof ROIs [74] In their work nanoceria prevented ROI-induced apoptosis and intracellular accumulation of ROIin cultured retinal neurons in the presence of H

2O2 They

further demonstrated that nanoceria injected into the eyes ofrats protected retina photoreceptor cells from light-induceddegeneration The study by Hirst et al also demonstratedthat nanoceria could be used for anti-inflammation byelimination of the radical oxygen species in J774A1 murinemacrophage cells [75]

Superparamagnetic iron oxide (SPIO) nanoparticles havebeen employed to promote growth of stem cells Huanget al reported that Ferucarbotran a commercialized SPIOcould promote cell growth in humanmesenchymal stem cells(hMSCs) by diminishing intracellular H

2O2and also accel-

erate cell cycle progression [76] In this report the intrinsicperoxidase-like activity of SPIO dramatically reduced intra-cellular H

2O2after internalization into hMSCs as well as

free iron ions released from lysosomal degradation of SPIO-affected cell cycle control molecules

35 Environmental Engineering Recently environmentalproblems such as water and air pollution food safety and

public health have become growing concerns in societyIn addition to the aforementioned applications nanozyme-based techniques have been explored for use in the field ofenvironmental technology

351 Pollutant Detection Ding et al developed a simpleand rapid colorimetric method for detecting melamine anorganic nitrogenous compound which is toxic when swal-lowed and has been illegally added to dairy products [77]The principle of this method is as follows Melamine inhibitsthe catalytic oxidation of colorimetric substrates (ABTS) byMNPs in the presence of H

2O2 because it competitively

reacts with H2O2 forming an additional compound Conse-

quently the intensity of the ABTS color signal was dependenton the concentration of melamine On the basis of thisreaction a colorimetric systemusingMNPs could enable easydetection by the naked eye of concentrations of melamineabove safety limits in dairy products

Nanocomposite-entrapping MNPs and oxidase in meso-porous carbonwere used to detect several phenol compoundsamperometrically such as phenol cresol and cathechol[49] These phenol compounds produced a concentration-dependent increase of cathodic current in this system whichmay have great potential in the field of environmentalmonitoring

352 Pollutant Removal Although there have been manymethods for removal of industrial dyestuffs such as absorp-tion precipitation and ultrasonic decomposition they couldnot efficiently degrade organic pollutants in wastewaterNanozyme-based methods have been found to be a power-ful cost-effective and simple method for degradation andmineralization of organic dyes from industrial processesMost prominently MNPs such as peroxidase have beeninvestigated for degradation of organic pollutants such asmethylene blue phenol and rhodamine B A MNP-baseddegradation method offers distinct advantages over existingdegradation methods which use HRP such as lower costhigh stability and reusability MNPs-H

2O2could remove

85 of phenol from aqueous solution within three hours[78] The MNPs-based degradation showed higher efficiencycompared to HRP-based degradation and stability in a broadrange of temperatures (5ndash90∘C) leading to ease of storageFurthermore MNPs could be captured by the application ofan external field and recycled for five rounds retaining almost100 of their activity Removal of methylene blue by MNPs-H2O2coupled method has also been successfully performed

by Jiang et al [79] It was observed that 96ofmethylene bluewas degraded in 15 minutes at optimized condition

Gao et al reported that MNPs-H2O2system could

degrade biofilm and kill resident bacteria [80] Biofilm espe-cially formed by Pseudomonas aeruginosa occurs in hospitalwater systems and medical devices with high frequencybecoming a common cause of nosocomial infection [81]In this report MNPs-H

2O2system exhibited significantly

higher efficiency than the use of H2O2in degradation of

biofilm The authors confirmed that additional free hydroxylradicals generated by MNP catalysis of H

2O2facilitated

the oxidative cleavage of biofilm components (nucleic acids

Journal of Nanomaterials 7

Table1Va

rious

applicationstu

dies

basedon

nano

zymes

Applicationfield

Nanozym

esAc

tivity

Detectio

nmetho

dDetails

Ref

Biosensor

MNPs

Peroxidase

Colorim

etric

H2O2biosensor

[9]

AuNPs

Glucose

oxidase

Colorim

etric

Nucleicacid

detection

[15]

Carboxyl-m

odified

graphene

oxide

Peroxidase

Colorim

etric

H2O2andglucoseb

iosensor

[23]

MNPs

Peroxidase

Colorim

etric

H2O2andglucoseb

iosensor

[44]

MNPs

Peroxidase

Colorim

etric

H2O2biosensor

[45]

MNPs

Peroxidase

Colorim

etric

H2O2biosensor

[46]

AuNPs

Peroxidase

Colorim

etric

H2O2andglucoseb

iosensor

[47]

MNPs

Peroxidase

Electro

chem

ical

Glucose

biosensor

[48]

MNPs

(with

oxidaseinmesop

orou

scarbo

n)Peroxidase

Electro

chem

ical

Glucose

biosensor

[49]

MNPs

(with

oxidaseinmesop

orou

ssilica)

Peroxidase

Colorim

etric

Glucose

andcholesterolbiosensor

[50]

MNPs

(with

oxidaseinmesop

orou

ssilica)

Peroxidase

Colorim

etric

Galactose

biosensor

[51]

MNPs

(with

oxidaseinmesop

orou

ssilica)

Peroxidase

Colorim

etric

Alcoh

olbiosensor

[52]

MNPs

Peroxidase

Colorim

etric

Nucleicacid

detection(Chlam

ydiatra

chom

atis)

[53]

CeO2NPs

Oxidase

Colorim

etric

Nucleicacid

detection(Chlam

ydiatra

chom

atis)

[56]

Chito

san-mod

ified

MNPs

with

thrombinaptamers

Peroxidase

Colorim

etric

Thrombindetection

[57]

Immun

oassay

MNPs

Peroxidase

Colorim

etric

Cardiactropo

ninI(Tn

I)detection

[9]

MNPs-PtN

Psin

mesop

orou

scarbo

nPeroxidase

Colorim

etric

Rotavirusa

ndHER

2detection

[33]

Graph

eneo

xide

Peroxidase

Colorim

etric

Prostatespecifica

ntigen

(PSA

)detectio

n[41]

Chito

san-mod

ified

MNPs

Peroxidase

Colorim

etric

Mou

seIgGandcarcinoembryonica

ntigen

detection

[63]

Prussia

nblue

mod

ified120574-Fe 2O3NPs

Peroxidase

Colorim

etric

IgGdetection

[64]

Ferritins

Peroxidase

Fluo

rometric

Avidin

andhu

man

ceruloplasmin

detection

[65]

MNPs

Peroxidase

Colorim

etric

Rotavirusa

ndHER

2detection

[66]

MNPs-PtN

Pson

graphene

oxide

Peroxidase

Colorim

etric

fluo

rometric

HER

2detectionandim

aging

[35]

Cancer

diagno

stics

(with

outimmun

ereactio

n)andtherapy

Poly(acrylicacid)-coated

CeO2NPs

Oxidase

Colorim

etric

Lung

cancer

celldetection

[13]

Poly(acrylicacid)-coated

CeO2NPs

Oxidase

Colorim

etric

Lung

andbreastcancer

celldetection

[69]

MagnetoferritinNPs

Peroxidase

Colorim

etric

fluo

rometric

Cancer

cellim

aging

[70]

CeO2NPs

Superoxide

dism

utase

Preventio

nof

retin

aldegeneratio

n[74]

CeO2NPs

Superoxide

dism

utase

Anti-infl

ammation

[75]

Superparam

agnetic

ironoxideN

PsPeroxidase

Prom

otionof

stem

cellgrow

th[76]

Environm

ental

engineering

MNPs

(with

oxidaseinmesop

orou

scarbo

n)Peroxidase

Electro

chem

ical

Phenolcresolandcathecho

ldetectio

n[49]

MNPs

Peroxidase

Colorim

etric

Mela

mined

etectio

n[77]

MNPs

Peroxidase

Removalof

phenol

[78]

MNPs

Peroxidase

Removalof

methylene

blue

[79]

MNPs

Peroxidase

Biofi

lmdegradation

[80]

8 Journal of Nanomaterials

proteins and polysaccharides) as well as killing residentbacteria

4 Conclusions and Future Research Aspects

Nanozymes have recently emerged as a potent alternativeto natural enzymes As discussed above although they arestill in the initial stages of research their use has developedsubstantially inmanydifferent detection and treatmentmeth-ods for biomolecules (Table 1) Despite the advantages ofnanozymes such as their low cost high stability robustnessease of mass production and long-term storability thereare several challenges to be tackled for practical use Firstlymost nanozymes have low activity compared to naturalenzymes Even if the nanomaterial itself is highly activeadditional coating and surface modification can decrease itsperformance Therefore development of novel nanozymesexhibiting high activity and appropriate surface-modificationtechniques are the emerging issues in the field of nanozymesNanozymes also have low selectivity to targets owing to theabsence of active sites where a substrate molecule binds andundergoes a chemical reaction in a natural enzyme Althoughresearchers have designed various types of surface-modifiednanozymes with polymers nucleic acids and antibodiesto provide selectivity mimicking natural enzymes this isstill insufficient for use in practical applications Toxicity ofnanozymes to humans and the ecosystem is also an essentialissue to be solved in regard to environmental and therapeuticapplications

In order for nanozymes to be positioned as a novelsource technology by efficiently overcoming the limitationsof natural enzymes we offer the following suggestions Thedevelopment of new nanozymes with higher activity andother positive properties than existing nanozymes is requiredWhile traditional research on developing nanozymes hasbeen performed by random screening of the enzyme-like activities of existing unspecified nanomaterials futureresearch will follow a strategy of rational screening ofenzyme-like activity based on those atomic compositionswhich are envisaged to catalyze enzymatic reactions Fur-thermore a strategy to prepare composites can be expectedto resolve the current major limitations of nanozymes oflow catalytic activity by exploiting their synergistic effectto facilitate electron transfer between composite materialsduring redox reaction Bioinspired synthesis of nanozymesalso provides an option to prepare nontoxic nanozymesby effectively circumventing the use of toxic chemicals inconventional chemical synthesis thereby accelerating theiruse in therapeutic applications Finally the developmentof novel surface engineering technology that can makenanozymes selective to target substrates will be importantin this field With the abovementioned research projects weexpect nanozymes to be widely employed in a wide range ofapplications in the near future

Conflict of Interests

The authors declare no financial or commercial conflict ofinterests

Acknowledgments

This work was supported by the Basic Science ResearchProgram through theNational Research Foundation of Korea(NRF) funded by the Ministry of Science ICT amp FuturePlanning (NRF-2014R1A1A1006016) and by the Gachon Uni-versity research fund of 2014 (GCU-2014-0110)

References

[1] D L Nelson and M M Cox Lehninger Principles of Biochem-istry vol 6 chapter 6 W H Freeman New York NY USA2005

[2] Z Liu R Cai L Mao H Huang and W Ma ldquoHighly sensitivespectrofluorimetric determination of hydrogen peroxide with120573-cyclodextrin-hemin as catalystrdquo Analyst vol 124 no 2 pp173ndash176 1999

[3] R P Bonar-Law and J K M Sanders ldquoPolyol recognition bya steroid-capped porphyrin Enhancement and modulation ofmisfit guest binding by added water or methanolrdquo Journal of theAmerican Chemical Society vol 117 no 1 pp 259ndash271 1995

[4] X-M Huang M Zhu L-Y Mao and H-X Shen ldquoCat-alytic determination of hydrogen peroxide by using themolybdenum-porphyrin complex as a mimetic enzyme ofperoxidaserdquo Analytical Sciences vol 13 no 1 pp 145ndash147 1997

[5] L Fruk andCMNiemeyer ldquoCovalent hemin-DNAadducts forgenerating a novel class of artificial heme enzymesrdquoAngewandteChemiemdashInternational Edition vol 44 no 17 pp 2603ndash26062005

[6] Q Wang Z Yang X Zhang X Xiao C K Chang and B XuldquoA supramolecular-hydrogel-encapsulated hemin as an artifi-cial enzyme to mimic peroxidaserdquo Angewandte Chemie Inter-national Edition vol 46 no 23 pp 4285ndash4289 2007

[7] Z Genfa and P K Dasgupta ldquoHematin as a peroxidase sub-stitute in hydrogen peroxide determinationsrdquo Analytical Chem-istry vol 64 no 5 pp 517ndash522 1992

[8] H Wei and E Wang ldquoNanomaterials with enzyme-like char-acteristics (nanozymes) next-generation artificial enzymesrdquoChemical Society Reviews vol 42 no 14 pp 6060ndash6093 2013

[9] L Gao J Zhuang LNie et al ldquoIntrinsic peroxidase-like activityof ferromagnetic nanoparticlesrdquo Nature Nanotechnology vol 2no 9 pp 577ndash583 2007

[10] R Polsky R Gill L Kaganovsky and I Willner ldquoNucleic acid-functionalized Pt nanoparticles catalytic labels for the ampli-fied electrochemical detection of biomoleculesrdquo AnalyticalChemistry vol 78 no 7 pp 2268ndash2271 2006

[11] T Li Y Du and E Wang ldquoPolyethyleneimine-functionalizedplatinum nanoparticles with high electrochemiluminescenceactivity and their applications to amplified analysis of bio-moleculesrdquo ChemistrymdashAn Asian Journal vol 3 no 11 pp1942ndash1948 2008

[12] W W He Y Liu J S Yuan et al ldquoAuPt nanostructures asoxidase and peroxidase mimetics for use in immunoassaysrdquoBiomaterials vol 32 no 4 pp 1139ndash1147 2011

[13] A Asati S Santra C Kaittanis S Nath and J M PerezldquoOxidase-like activity of polymer-coated cerium oxide nano-partielesrdquo Angewandte ChemiemdashInternational Edition vol 48no 13 pp 2308ndash2312 2009

[14] W J Luo C F Zhu S Su et al ldquoSelf-catalyzed self-limitinggrowth of glucose oxidase-mimicking gold nanoparticlesrdquo ACSNano vol 4 no 12 pp 7451ndash7458 2010

Journal of Nanomaterials 9

[15] X Zheng Q Liu C Jing et al ldquoCatalytic gold nanoparticles fornanoplasmonic detection of DNA hybridizationrdquo AngewandteChemie International Edition vol 50 no 50 pp 11994ndash119982011

[16] Y J Long Y F Li Y Liu J J Zheng J Tang and C JHuang ldquoVisual observation of the mercury-stimulated peroxi-dase mimetic activity of gold nanoparticlesrdquo Chemical Commu-nications vol 47 no 43 pp 11939ndash11941 2011

[17] W Chen J Chen Y-B Feng et al ldquoPeroxidase-like activityof water-soluble cupric oxide nanoparticles and its analyticalapplication for detection of hydrogen peroxide and glucoserdquoAnalyst vol 137 no 7 pp 1706ndash1712 2012

[18] W Luo Y-S Li J Yuan et al ldquoUltrasensitive fluorometricdetermination of hydrogen peroxide and glucose by usingmultiferroic BiFeO

3nanoparticles as a catalystrdquo Talanta vol 81

no 3 pp 901ndash907 2010[19] S H He W B Shi X D Zhang J A Li and Y M Huang ldquo120573-

Cyclodextrins-based inclusion complexes of CoFe2O4magnetic

nanoparticles as catalyst for the luminol chemiluminescencesystem and their applications in hydrogen peroxide detectionrdquoTalanta vol 82 no 1 pp 377ndash383 2010

[20] W B Shi X D Zhang S H He and Y M Huang ldquoCoFe2O4

magnetic nanoparticles as a peroxidasemimicmediated chemi-luminescence for hydrogen peroxide and glucoserdquo ChemicalCommunications vol 47 no 38 pp 10785ndash10787 2011

[21] Y W Fan and Y M Huang ldquoThe effective peroxidase-likeactivity of chitosan-functionalized CoFe

2O4nanoparticles for

chemiluminescence sensing of hydrogen peroxide and glucoserdquoAnalyst vol 137 no 5 pp 1225ndash1231 2012

[22] A K Dutta S K Maji D N Srivastava et al ldquoSynthesis ofFeS and FeSe nanoparticles from a single source precursor astudy of their photocatalytic activity peroxidase-like behaviorand electrochemical sensing of H

2O2rdquo ACS Applied Materials

and Interfaces vol 4 no 4 pp 1919ndash1927 2012[23] Y Song K Qu C Zhao J Ren and X Qu ldquoGraphene oxide

intrinsic peroxidase catalytic activity and its application toglucose detectionrdquoAdvancedMaterials vol 22 no 19 pp 2206ndash2210 2010

[24] Y Song X Wang C Zhao K Qu J Ren and X Qu ldquoLabel-free colorimetric detection of single nucleotide polymorphismby using single-walled carbon nanotube intrinsic peroxidase-like activityrdquo ChemistrymdashA European Journal vol 16 no 12 pp3617ndash3621 2010

[25] Y Guo J Li and S Dong ldquoHemin functionalized graphenenanosheets-based dual biosensor platforms for hydrogen per-oxide and glucoserdquo Sensors and Actuators B Chemical vol 160no 1 pp 295ndash300 2011

[26] J Xie X Zhang H Wang H Zheng Y Huang and J XieldquoAnalytical and environmental applications of nanoparticles asenzyme mimeticsrdquo TrACmdashTrends in Analytical Chemistry vol39 pp 114ndash129 2012

[27] A K Gupta and M Gupta ldquoSynthesis and surface engineeringof iron oxide nanoparticles for biomedical applicationsrdquoBioma-terials vol 26 no 18 pp 3995ndash4021 2005

[28] J Mu Y Wang M Zhao and L Zhang ldquoIntrinsic peroxidase-like activity and catalase-like activity of Co

3O4nanoparticlesrdquo

Chemical Communications vol 48 no 19 pp 2540ndash2542 2012[29] Y Wan P Qi D Zhang J Wu and Y Wang ldquoMan-

ganese oxide nanowire-mediated enzyme-linked immunosor-bent assayrdquo Biosensors and Bioelectronics vol 33 no 1 pp 69ndash74 2012

[30] R Andre F Natalio M Humanes et al ldquoV2O5nanowires

with an intrinsic peroxidase-like activityrdquo Advanced FunctionalMaterials vol 21 no 3 pp 501ndash509 2011

[31] W Chen J Chen A-L Liu L-M Wang G-W Li and X-H Lin ldquoPeroxidase-like activity of cupric oxide nanoparticlerdquoChemCatChem vol 3 no 7 pp 1151ndash1154 2011

[32] Y-L DongH-G Zhang Z U Rahman et al ldquoGraphene oxide-Fe3O4magnetic nanocomposites with peroxidase-like activity

for colorimetric detection of glucoserdquo Nanoscale vol 4 no 13pp 3969ndash3976 2012

[33] M I Kim Y Ye M-A Woo J Lee and H G Park ldquoA highlyefficient colorimetric immunoassay using a nanocompositeentrapping magnetic and platinum nanoparticles in orderedmesoporous carbonrdquo Advanced Healthcare Materials vol 3 no1 pp 36ndash41 2014

[34] J Liu X Hu S Hou et al ldquoAuPt coreshell nanorods withperoxidase- and ascorbate oxidase-like activities for improveddetection of glucoserdquo Sensors and Actuators B Chemical vol166-167 pp 708ndash714 2012

[35] M I Kim M S Kim M-AWoo et al ldquoHighly efficient colori-metric detection of target cancer cells utilizing superior catalyticactivity of graphene oxide-magnetic-platinum nanohybridsrdquoNanoscale vol 6 no 3 pp 1529ndash1536 2014

[36] M Liu H Zhao S Chen H Yu and X Quan ldquoInterface engi-neering catalytic graphene for smart colorimetric biosensingrdquoACS Nano vol 6 no 4 pp 3142ndash3151 2012

[37] Y Ye T Kong X Yu YWu K Zhang and XWang ldquoEnhancednonenzymatic hydrogen peroxide sensing with reducedgraphene oxideferroferric oxide nanocompositesrdquo Talantavol 89 pp 417ndash421 2012

[38] R Cui Z Han and J-J Zhu ldquoHelical carbon nanotubesintrinsic peroxidase catalytic activity and its application forbiocatalysis and biosensingrdquo ChemistrymdashA European Journalvol 17 no 34 pp 9377ndash9384 2011

[39] M Liu H Zhao S Chen H Yu and X Quan ldquoStimuli-responsive peroxidase mimicking at a smart graphene inter-facerdquo Chemical Communications vol 48 no 56 pp 7055ndash70572012

[40] S Liu J Tian L Wang Y Luo and X Sun ldquoA general strategyfor the production of photoluminescent carbon nitride dotsfrom organic amines and their application as novel peroxidase-like catalysts for colorimetric detection of H

2O2and glucoserdquo

RSC Advances vol 2 no 2 pp 411ndash413 2012[41] F Qu T Li and M Yang ldquoColorimetric platform for visual

detection of cancer biomarker based on intrinsic peroxidaseactivity of graphene oxiderdquo Biosensors and Bioelectronics vol26 no 9 pp 3927ndash3931 2011

[42] W Shi QWang Y Long et al ldquoCarbon nanodots as peroxidasemimetics and their applications to glucose detectionrdquo ChemicalCommunications vol 47 no 23 pp 6695ndash6697 2011

[43] X Wang K Qu B Xu J Ren and X Qu ldquoMulticolorluminescent carbon nanoparticles synthesis supramolecularassembly with porphyrin intrinsic peroxidase-like catalyticactivity and applicationsrdquo Nano Research vol 4 no 9 pp 908ndash920 2011

[44] H Wei and E Wang ldquoFe3O4magnetic nanoparticles as per-

oxidase mimetics and their applications in H2O2and glucose

detectionrdquo Analytical Chemistry vol 80 no 6 pp 2250ndash22542008

[45] Q Chang KDeng L ZhuG Jiang C Yu andH Tang ldquoDeter-mination of hydrogen peroxide with the aid of peroxidase-like

10 Journal of Nanomaterials

Fe3O4magnetic nanoparticles as the catalystrdquo Microchimica

Acta vol 165 no 3-4 pp 299ndash305 2009[46] Z Jiang L Kun H Ouyang A Liang and H Jiang ldquoA simple

and sensitive fluorescence quenching method for the determi-nation of H

2O2using rhodamine B and Fe

3O4nanocatalystrdquo

Journal of Fluorescence vol 21 no 5 pp 2015ndash2020 2011[47] Y Jv B Li andR Cao ldquoPositively-charged gold nanoparticles as

peroxidiase mimic and their application in hydrogen peroxideand glucose detectionrdquo Chemical Communications vol 46 no42 pp 8017ndash8019 2010

[48] K Wang J-J Xu D-C Sun H Wei and X-H Xia ldquoSelectiveglucose detection based on the concept of electrochemicaldepletion of electroactive species in diffusion layerrdquo Biosensorsand Bioelectronics vol 20 no 7 pp 1366ndash1372 2005

[49] M I Kim Y Ye B Y Won S Shin J Lee and H G Park ldquoAhighly efficient electrochemical biosensing platform by employ-ing conductive nanocomposite entrapping magnetic nano-particles and oxidase in mesoporous carbon foamrdquo AdvancedFunctional Materials vol 21 no 15 pp 2868ndash2875 2011

[50] M I Kim J Shim T Li J Lee and H G Park ldquoFabrica-tion of nanoporous nanocomposites entrapping Fe

3O4mag-

netic nanoparticles and oxidases for colorimetric biosensingrdquoChemistrymdashAEuropean Journal vol 17 no 38 pp 10700ndash107072011

[51] M I Kim J Shim T Li et al ldquoColorimetric quantificationof galactose using a nanostructured multi-catalyst systementrapping galactose oxidase and magnetic nanoparticles asperoxidasemimeticsrdquoAnalyst vol 137 no 5 pp 1137ndash1143 2012

[52] M I Kim J Shim H J Parab S C Shin J Lee and H G ParkldquoA convenient alcohol sensor using one-pot nanocompositeentrapping alcohol oxidase and magnetic nanoparticles as per-oxidase mimeticsrdquo Journal of Nanoscience and Nanotechnologyvol 12 no 7 pp 5914ndash5919 2012

[53] K S Park M I Kim D-Y Cho and H G Park ldquoLabel-free colorimetric detection of nucleic acids based on target-induced shielding against the peroxidase-mimicking activity ofmagnetic nanoparticlesrdquo Small vol 7 no 11 pp 1521ndash1525 2011

[54] J A Brinkman M Z Rahmani W E Jones A K Chaturvediand M E Hagensee ldquoOptimization of PCR based detection ofhuman papillomavirus DNA from urine specimensrdquo Journal ofClinical Virology vol 29 no 4 pp 230ndash240 2004

[55] L Hafner K Beagley and P Timms ldquoChlamydia trachomatisinfection host immune responses and potential vaccinesrdquoMucosal Immunology vol 1 no 2 pp 116ndash130 2008

[56] M I Kim K S Park and H G Park ldquoUltrafast colorimetricdetection of nucleic acids based on the inhibition of the oxidaseactivity of cerium oxide nanoparticlesrdquo Chemical Communica-tions vol 50 no 67 pp 9577ndash9580 2014

[57] Z Zhang Z Wang X Wang and X Yang ldquoMagneticnanoparticle-linked colorimetric aptasensor for the detection ofthrombinrdquo Sensors and Actuators B Chemical vol 147 no 2 pp428ndash433 2010

[58] B W Blais and A Martinez-Perez ldquoDetection of groupD salmonellae including Salmonella enteritidis in eggs bypolymyxin-based enzyme-linked immunosorbent assayrdquo Jour-nal of Food Protection vol 71 no 2 pp 392ndash396 2008

[59] V Tripathi S Nara S K Chaube et al ldquoDevelopment ofrapid and sensitive one-step direct enzyme linked immunosor-bent assay for 17-120572-OH-progesterone in serumrdquo Journal ofImmunoassay and Immunochemistry vol 29 no 2 pp 117ndash1272008

[60] K DMcReynolds M J Hadd and J Gervay-Hague ldquoSynthesisof biotinylated glycoconjugates and their use in a novel ELISAfor direct comparison ofHIV-1 gp120 recognition ofGalCer andrelated carbohydrate analoguesrdquo Bioconjugate Chemistry vol10 no 6 pp 1021ndash1031 1999

[61] H Hocini S Iscaki J-P Bouvet M D Kazatchkine and LBelec ldquoAn ELISA method to measure total and specific humansecretory IgA subclasses based on selective degradation by IgA1-proteaserdquo Journal of Immunological Methods vol 235 no 1-2pp 53ndash60 2000

[62] L Micheli S Di Stefano D Moscone et al ldquoProduction ofantibodies and development of highly sensitive formats ofenzyme immunoassay for saxitoxin analysisrdquo Analytical andBioanalytical Chemistry vol 373 no 8 pp 678ndash684 2002

[63] L Gao J Wu S Lyle K Zehr L Cao and D Gao ldquoMagnetitenanoparticle-linked immunosorbent assayrdquo Journal of PhysicalChemistry C vol 112 no 44 pp 17357ndash17361 2008

[64] X-Q Zhang S-W Gong Y Zhang T Yang C-YWang andNGu ldquoPrussian blue modified iron oxide magnetic nanoparticlesand their high peroxidase-like activityrdquo Journal of MaterialsChemistry vol 20 no 24 pp 5110ndash5116 2010

[65] Z Tang H Wu Y Zhang Z Li and Y Lin ldquoEnzyme-mimicactivity of ferric nano-core residing in ferritin and its biosensingapplicationsrdquo Analytical Chemistry vol 83 no 22 pp 8611ndash8616 2011

[66] M-A Woo M I Kim J H Jung K S Park T S Seoand H G Park ldquoA novel colorimetric immunoassay utilizingthe peroxidase mimicking activity of magnetic nanoparticlesrdquoInternational Journal of Molecular Sciences vol 14 no 5 pp9999ndash10014 2013

[67] V H C Bramwell G S Doig A B Tuck et al ldquoChangesover time of extracellular domain of HER2 (ECDHER2) serumlevels have prognostic value in metastatic breast cancerrdquo BreastCancer Research andTreatment vol 114 no 3 pp 503ndash511 2009

[68] K S Asgeirsson A Agrawal C Allen et al ldquoSerum epidermalgrowth factor receptor and HER2 expression in primary andmetastatic breast cancer patientsrdquo Breast Cancer Research vol9 no 6 article R75 2007

[69] A Asati C Kaittanis S Santra and J M Perez ldquoPH-tunableoxidase-like activity of cerium oxide nanoparticles achievingsensitive fluorigenic detection of cancer biomarkers at neutralpHrdquo Analytical Chemistry vol 83 no 7 pp 2547ndash2553 2011

[70] K L Fan C Q Cao Y X Pan et al ldquoMagnetoferritinnanoparticles for targeting and visualizing tumour tissuesrdquoNature Nanotechnology vol 7 no 7 pp 459ndash464 2012

[71] S Beatty H-H Koh M Phil D Henson and M BoultonldquoThe role of oxidative stress in the pathogenesis of age-relatedmacular degenerationrdquo Survey of Ophthalmology vol 45 no 2pp 115ndash134 2000

[72] C Korsvik S Patil S Seal and W T Self ldquoSuperoxidedismutase mimetic properties exhibited by vacancy engineeredceria nanoparticlesrdquo Chemical Communications no 10 pp1056ndash1058 2007

[73] E G Heckert A S Karakoti S Seal andW T Self ldquoThe role ofcerium redox state in the SOD mimetic activity of nanoceriardquoBiomaterials vol 29 no 18 pp 2705ndash2709 2008

[74] J Chen S Patil S Seal and J F McGinnis ldquoRare earthnanoparticles prevent retinal degeneration induced by intracel-lular peroxidesrdquo Nature Nanotechnology vol 1 no 2 pp 142ndash150 2006

Journal of Nanomaterials 11

[75] S M Hirst A S Karakoti R D Tyler N Sriranganathan SSeal and C M Reilly ldquoAnti-inflammatory properties of ceriumoxide nanoparticlesrdquo Small vol 5 no 24 pp 2848ndash2856 2009

[76] D-M Huang J-K Hsiao Y-C Chen et al ldquoThe promotion ofhuman mesenchymal stem cell proliferation by superparamag-netic iron oxide nanoparticlesrdquo Biomaterials vol 30 no 22 pp3645ndash3651 2009

[77] N Ding N Yan C Ren and X Chen ldquoColorimetric determi-nation of melamine in dairy products by Fe

3O4Magnetic nano-

particles-H2O2-ABTS detection systemrdquo Analytical Chemistry

vol 82 no 13 pp 5897ndash5899 2010[78] J Zhang J Zhuang L Gao et al ldquoDecomposing phenol by the

hidden talent of ferromagnetic nanoparticlesrdquo Chemospherevol 73 no 9 pp 1524ndash1528 2008

[79] J Z Jiang J Zou L H Zhu L Huang H Jiang and YZhang ldquoDegradation of methylene blue with H

2O2activated

by peroxidase-like Fe3O4magnetic nanoparticlesrdquo Journal of

Nanoscience and Nanotechnology vol 11 no 6 pp 4793ndash47992011

[80] L Gao K M Giglio J L Nelson H Sondermann and AJ Travis ldquoFerromagnetic nanoparticles with peroxidase-likeactivity enhance the cleavage of biological macromolecules forbiofilm eliminationrdquo Nanoscale vol 6 no 5 pp 2588ndash25932014

[81] K Vickery A Pajkos and Y Cossart ldquoRemoval of biofilmfrom endoscopes evaluation of detergent efficiencyrdquo AmericanJournal of Infection Control vol 32 no 3 pp 170ndash176 2004

Submit your manuscripts athttpwwwhindawicom

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CorrosionInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Polymer ScienceInternational Journal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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International Journal of

Biomaterials

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Advances in

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materials

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Journal ofNanomaterials

Page 3: Review Article Recent Research Trends and Future …downloads.hindawi.com/journals/jnm/2015/756278.pdfnovel biosensor, immunoassay, cancer diagnostics, therapeutics, and environmental

Journal of Nanomaterials 3

cobalt oxide nanoparticles (Co3O4NPs) [28] manganese

dioxide nanoparticles (MnO2NPs) [29] vanadiumpentoxide

nanoparticles (V2O5NPs) [30] and CuONPs [31] Generally

metal oxide-based nanozymes with peroxidase-like activityhave been those most widely investigated by researchersowing to their convenience for constructing amperometricand colorimetric detection systems by utilizing the capabilityof peroxidase to catalyze certain substrates which generatethe corresponding electric and colorimetric signal in thepresence of hydrogen peroxide (H

2O2) Herein we focus

on colorimetric detection systems utilizing peroxidase-likenanozymes and associated applications

22 Metal-Based Nanozymes Metal-based nanozymes suchas Au NPs and Pt NPs have been discovered to pos-sess the catalytic activities of oxidase peroxidase catalaseand SOD In addition to the single nanoparticle systemmentioned above nanocomposites which combine a metal-based nanozyme with other nanozymes have been alsointensively developed including Fe

3O4-graphene oxide (GO)

[32] Fe3O4-Pt [33] Au-Pt [34] and GO-Fe

3O4-Pt [35]

nanocomposites Surprisingly it was reported that metal-based nanozymes often exhibit synergistic effects whichsignificantly enhance catalytic performance when coupledwith other nanozymes as a composite [33]

23 Carbon-Based Nanozymes Carbon-based nanozymessuch as fullerene carbon nanotube graphene oxide andcarbon dot are also attracting great interest owing to theirunique enzyme-mimicking activities [23ndash25 36ndash43] Theyhave been found to possess peroxidase and SOD-mimickingabilities and are widely utilized as signaling agents forsignal amplification and detection of analytes in the field ofbiosensors and immunoassays

3 Recent Applications

31 Biosensors In recent time horseradish peroxidase(HRP) which can catalyze the oxidation of a variety ofsubstrates by H

2O2 has been one of the most commonly

used enzymes for the construction of biosensors In spiteof its high catalytic efficiency HRP-based biosensors havecritical problems in that the catalytic activity of HRP is proneto degradation in long-term storage and harsh conditionsthereby leading to errors in the process of sensing To solvethis problem a peroxidase-like nanozyme which is highlyrobust against environmental conditions is utilized in placeof HRP providing a cost-effective method of fabrication ofbiosensors

311 H2O2 Detection H2O2 detection plays an essential rolein the fields of biologymedicine environmental engineeringand food industry Since H

2O2 a product of an incompletely

reduced metabolite of oxygen is generated as a by-productof various biological pathways and is a contaminant inseveral industrial products and wastes H

2O2detection is of

practical importance in the field of biosensors With sub-stantial progress in biosensing technology various methodsfor H2O2detection have been reported Among them is the

colorimetric signal readout strategy based on a redox reac-tion between HRP and colorimetric substrates such as 221015840-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS)and 331015840551015840-tetramethylbenzidine (TMB) This strategy hasbeen actively developed due to its high sensitivity selectiv-ity and simplicity for detecting H

2O2 However since the

colorimetric detection method using HRP has problems oflow stability and high cost nanozymes showing peroxidase-like activity have been intensively utilized to resolve thesedrawbacks Beginning with the remarkable discovery thatMNPs exhibit intrinsic peroxidase-like activity [9] manyresearchers have focused on the development of novel H

2O2

detection methods employing various nanozymes Here wediscuss recent applications of various nanozymes in H

2O2

detectionAfter Yanrsquos report H

2O2detection methods with MNPs

(used as peroxidase-like nanozymes) were further developedby Wei and Wang [44] This research outlined a colorimetricdetection method for H

2O2 in which MNPs were used to

catalyze the oxidation of ABTS in the presence of H2O2

The catalytic oxidation of ABTS with H2O2generates green-

colored products by which H2O2can be detected by the

naked eyeThey noted that ABTS could be oxidized by H2O2

in the absence of any catalysts but demonstrated that thepresence ofMNPs gave a 320 higher response of absorptionspectra when compared with the absence of MNPs Not onlythe peroxidase-like catalytic activity of Fe

3O4MNPs but also

their high stability in rough conditions (pH and temperature)was confirmed with additional investigations

Based on the colorimetric detection method abovemany approaches have proceeded by varying the colori-metric substrates and nanozymes used NN-Dimethyl-p-phenylenediamine sulfate (DPD) was used as a colorimetricsubstrate in place of ABTS [45] The DPD-MNPs analyticalsystem showed several advantages (lower operating temper-ature and detection limit and higher sensitivity) over thesystem using ABTS because DPD is more easily oxidized byH2O2than ABTS and because oxidized DPD (DPD+) pro-

duces a colored product with a strong absorption maximumat 550 nm Aside from the signal-on colorimetric methodabove Jiangrsquos group has developed a new type of fluorescencemethod using rhodamine B (RhB) as a substrate [46] Inthis method MNPs catalyze H

2O2to form the radical OH

which can oxidize RhB to form colorless and nonfluorescentproducts In short the more the H

2O2exists the weaker the

fluorescence intensity of RhB isOther nanozymes have been also reported to detect

H2O2 Au NPs have been discovered to possess intrinsic

peroxidase-like activity [47] Caorsquos studies reported thatpositively charged Au NPs can catalyze the oxidation of TMBby H2O2 Carboxyl-modified graphene oxide was shown to

possess intrinsic peroxidase-like activity that can catalyze thereaction of TMB in the presence of H

2O2to produce a blue-

color reaction [23] Concentrations as low as 5 times 10minus8mol Lminus1H2O2were detected with a linear range from 5 times 10minus8 to 1 times

10minus6mol Lminus1

312 Glucose Detection Peroxidase-like nanozymes coupledwith glucose oxidase (GOx) have been frequently employed

4 Journal of Nanomaterials

in the construction of glucose biosensors Wang et al devel-oped a colorimetric glucose detection platform by combiningthe catalytic oxidation of glucose with GOx and the catalyticreaction of ABTS withMNPs [48] Glucose concentrations aslow as 30 120583M were detected with a linear range from 50 120583Mto 1mM in this study

There have been several reports of an electrochemi-cal biosensing platform using GOx-coupled nanozymes Ahighly efficient and robust electrochemical biosensing strat-egy employing a nanocomposite harboring GOx-couplednanozymes was developed by our group [49] In this reportMNPs and GOx were entrapped in the pores of mesoporouscarbon in which GOx immobilized in the nanocompositegenerates H

2O2which then is directly reduced to H

2O

with the electrocatalytic reduction mediated by MNPs Thissystem showed a linear range of (05 to 10) times 10minus3M and adetection limit of 02 times 10minus3M

313 Oxidase-Coupled Methods (Except Glucose Oxidase)On the basis of the mechanism of glucose detection aboveseveral different oxidases have also been coupled withnanozymes for the fabrication of biosensing platforms Ananostructured multicatalyst system consisting of MNPsand cholesterol oxidase entrapped in large-pore-sized meso-porous silica has been developed for convenient colorimetricdetection of cholesterol [50] This multicatalyst system iscomposed of MNPs incorporated in the wall of mesocellularsilica pores forming magnetic mesoporous silica (MMS)and cholesterol oxidases In this system cholesterol oxidaseimmobilized in the MMS promotes a reaction with choles-terol to generate H

2O2 which subsequently activates MNPs

in the mesocellular silica pores to convert a colorimetric sub-strate into a colored product The result of this investigationshows the cholesterol oxidase-coupled method to have highselectivity and sensitivity (limit of detection LOD of 5120583Min the linear range from 10 to 250 120583M) for the detection ofcholesterol A colorimetricmethod for detection of galactosewhich utilizes a nanostructured multicatalyst system consist-ing of MNPs and galactose oxidase has also been reported[51] The clinical applicability of this multicatalytic systemwas successfully evaluated as a promising analytical tool todiagnose galactosemia by determining the concentration ofgalactose eluted from the dried blood specimens provided byclinical hospitals

Apart from the above oxidases alcohol oxidase has beenused in a colorimetric biosensor for quantification of ethanoland methanol [52] The nanocomposite system utilizingalcohol oxidase entrapped in mesocellular silica with MNPsprovided a rapid and convenient platform for analysis ofalcohol with high stability and reusability It showed a linearconcentration range from 100 to 500120583M with a detectionlimit as low as 25 120583M

314 OtherMethods Recently peroxidase-mimicking nano-materials such as MNPs CeO

2NPs and Au NPs [15] have

been employed for new methods of DNA detection A label-free colorimetric detection method for nucleic acids hasbeen developed [53] In this method the target DNA inthe sample which is amplified by polymerase chain reaction

(PCR) is directly adsorbed on the surface of the MNPs dueto electrostatic interactions between the negatively chargedphosphate backbone and the positively charged surface of theNPs thereby inducing a shielding effect against colorimetricsubstrate binding to MNPs The peroxidase activity of MNPswill decrease due to the DNA-induced shielding so thatthe intensity of the color signal will also be significantlyreduced Using this detection method researchers succes-sively detectedChlamydia trachomatis in humanurine whichis one of the common bacteria causing sexually transmitteddisease (STD) [54 55] CeO

2NPs were also employed in a

label-free colorimetric method for detecting C trachomatisand this method provided ultrafast detection of the targetnucleic acid (target nucleic acids can be determined withina few minutes) [56]

A novel biosensing format using aptamers has been devel-oped by several researchers based on the fact that aptamerswhich are ssDNA or ssRNA that can specifically bind to atarget can replace antibodies for the specific recognition oftarget molecules A method using chitosan-modified MNPsconjugated with thrombin aptamers was reported by Zhangrsquosgroup [57] They constructed a sandwich-type assay for thedetection of thrombin with two thrombin aptamers Thisaptamer-based assay showed a linear detection range from 1to 100 nM and a detection limit of 1 nM of thrombin

32 Immunoassays Immunoassays have been used in hos-pitals laboratory medicine and research to improve thehealth and well-being of humans and animals Informationgained by clinical immunoassay testing has shortened thelength of hospital stays and decreased the severity of illnessby identifying and assessing the progression of diseasethereby leading to improved therapeutic choices In lifescience research immunoassays are used in the study ofbiological systems for tracking different proteins hormonesand antibodies In industry immunoassays are used to detectcontaminants in food and water and in quality control tomonitor specific molecules used during product processingHowever themost commonly used enzymes in immunoassayinclude horseradish peroxidase and alkaline phosphatase[58ndash62] which lose their enzymatic activities gradually overlong-term storage [63] To overcome these limits variousstudies on replacing natural enzymes have been reported andconsequently novel types of immunoassay using nanozymesin place of HRP have been developed

321 Sandwich or Antigen-Down Type Immunoassays Gaoand coworkers reported an immunoassay using chitosan-modified MNPs (CS-MNPs) as a replacement for HRP in thetraditional immunoassay [63] They provided protocols forantigen-down and sandwich immunoassays with CS-MNPsand detected mouse IgG and carcinoembryonic antigen(CEA) respectively Chitosan modified on the surface ofMNPs prevented aggregation of MNPs so that MNPs wereeasily dispersed in aqueous solutions Meanwhile aminogroups in the chitosan provided a convenient site for covalentlinking of antibodies to MNPs thereby replacing the linkageof HRP-conjugated antibodies to CS-MNP-conjugated anti-bodies in the immunoassay Capture-detection immunoassay

Journal of Nanomaterials 5

was also developed to detect CEA by employing themagneticproperties of CS-MNPs which facilitate capturing separat-ing and enriching antigens as well as redispersing the MNPaggregation in solution

Zhang and coworkers reported a novel immunoassayutilizing Prussian blue modified 120574-Fe

2O3NPs [64] Prus-

sian blue a dark blue pigment with the idealized formulaFe7(CN)18 was modified on the surface of 120574-Fe

2O3NPs due

to its excellent electrochemical behavior that accelerated elec-tron transfer and its catalytic properties that could catalyzethe reduction of H

2O2 Prussian blue modified 120574-Fe

2O3NPs

(PBMNPs) were next conjugated with staphylococcal proteinA (SPA) to bind to IgG immobilized in the well so thatPBMNPs could derive a colorimetric reaction in the presenceof TMB and H

2O2

Ferritins nanoscale globular protein cages encapsulatinga ferric core were used in immunoassay in Tang et alrsquos study[65] In this study ferritin showed a thermally stable and pH-tolerable enzyme-mimetic activity derived from the ferricnanocore of ferritin Two forms of immunoassay systemswere constructed antigen-down type and sandwich typeAvidin was selected as the target molecule of the antigen-down immunoassay and nitrated human ceruloplasmin asthe target molecule of the sandwich-type immunoassayTheyalso reported that the ferritins could be utilized in analyticalapplications such as H

2O2assay In their assay ferritin

oxidizes the p-HPPA in the presence of H2O2to generate

a fluorescent product This ferritin-based H2O2assay shows

a detection limit of 016 120583M and a linear detection range of40 120583M which is one-order higher sensitivity with a broaderlinear response range

Immunoassay systems for detection of rotavirus andbreast cancer have been developed [66] in which MNPsare conjugated to antibodies against rotaviruses and humanepidermal growth factor receptor 2 (HER2) In this sys-tem sandwich-type and antigen-down type immunoassaywere used to detect rotavirus and HER2 respectively Forthe detection of rotavirus rotavirus antibodies were firstimmobilized in a well and rotavirus bound to the immo-bilized antibody Subsequently MNP-conjugated antibodies(MNP-Abs) were added to the well in order to bind tocaptured rotaviruses Finally the peroxidase substrate TMBwas changed into blue-colored products in the presence ofH2O2 An antigen-down immunoassay system was used in

the case of breast cell detection which did not require priorimmobilization of antibodies in the bare well surface Breastcells were cultured in a well so that they adsorbed to thesurface of the well MNPs-Abs were then applied to the cell-cultured well followed by adding TMB and H

2O2to induce

a colorimetric reactionThis assay system displayed excellentspecificity sensitivity and linearity for quantitative detectionof the target molecules as well as the production of a colorsignal that could be detected by the naked eye

Based on the above system a nanocomposite-basedimmunoassay was also performed in which nanocompositeentrappingMNPs and Pt NPs in ordered mesoporous carbon(OMC) were utilized instead of HRP [33]This immunoassaygenerated significantly higher absorption intensity of colorsignal than the current ELISA and was able to quantify the

target antigen very rapidly within three minutes while theconventional ELISA requires several tens of minutes for colorsignal development [67 68] It showed a limit of detection(LOD) for HER2 of 15 ngmLminus1 in the linear range from 25 to100 ngmLminus1 The nanocomposite was found to have 50 timeshigher catalytic efficiency than that of free MNPs owing tothe high catalytic action of Pt NPs

Graphene oxide (GO) has been used in immunoassay as aperoxidase-mimicking nanozyme [41] Yanrsquos group developeda sandwich-type immunoassay for the detection of cancerbiomarker prostate specific antigen (PSA) In this work amagnetic bead (MB) was used to immobilize the primaryPSA antibody (Ab

1) and then a GO-conjugated secondary

antibody (Ab2) was applied in the presence of PSA Subse-

quentlyMB-Ab1was separated from the immunocomplex by

an external magnetic field and GO catalyzed the oxidation ofhydroquinone in the presence of H

2O2to generate a brown-

colored productConjugating both MNPs and Pt NPs on the surface of

GO enabled highly sensitive and rapid colorimetric detectionof the target cancer cell [35] In this work it was notablethat the electron transfer between MNPs and Pt NPs createsa synergistic effect significantly enhancing the catalyticperformance of MNPs-Pt NPs-GO nanohybrids Using thisimmunoassay system human breast adenocarcinoma cells(SKBR-3) which overexpressed HER2 were detected in fiveminutes with high specificity and sensitivity The LOD fortarget SKBR-3 cells was found to be about 100 cells in thelinear range from 100 to 1000 cells Moreover fluorescenceimaging of SKBR-3 was successfully performed with MNPs-Pt NPs-GO nanohybrids

322 Other Immunoassays By employing the superparam-agnetic property of MNPs a capture-detection immunoassaysystem has been developed by Gaorsquos group [63] In the proce-dure the CS-MNPs were conjugated with carcinoembryonicantibodies (anti-CEA M111147) and then mixed with thesample containing CEA After the CEA was captured byMNPs a magnetic field was applied to separate the MNPswhich had captured CEA Finally the MNPs capturing CEAwere injected into microplate wells coated with anothermonoclonal CEA antibody creating the sandwich formatThereby the MNPs prompted the generation of a color signalupon addition of colorimetric substrate and H

2O2to the

wells Cardiac troponin I (TnI) in serum a well-knownbiomarker for myocardial infarction was also detected by acapture-detection immunoassay utilizing the magnetism andperoxidase ability of MNPs [9]

33 Cancer Diagnostics without Immune Reaction Asidefrom immunoassay using antigen-antibody interaction othernovel assays using nanozymes have been developed partic-ularly for the diagnosis of tumor cells Asati and coworkersreported an assay for the determination of tumor cellswith poly(acrylic acid)-coated CeO

2NPs (nanoceria) as an

oxidase mimic [13] When the nanoparticles were conjugatedwith folic acid they bound to folate receptors on the tumorcell (A-549 lung cancer cells) due to high expression offolate receptors on the tumor cell surface Polymer-coated

6 Journal of Nanomaterials

nanoceria as an oxidase mimic made detection of tumorcells easier than with traditional immunoassay because itdirectly oxidized a colorimetric substrate to a colored productwithout H

2O2and additional steps to introduce an enzyme-

conjugated secondary antibody Further advances in thistechnology were also reported by employing a fluorescence-generating substrate ampliflu to detect target cancer cells ataround neutral pH [69]

Another interesting study to visualize target tumor tissueswithout the use of any additional targeting ligands hasalso been described [70] In this study peroxidase-like ironoxide nanoparticles were encapsulated inside a recombinanthuman heavy-chain ferritin (Hfn) protein shell which bindsto tumor cells that overexpress transferrin receptor 1The ironoxide cores catalyzed the oxidation of peroxidase substratesin the presence of H

2O2to produce the colorimetric signal

that was used to visualize tumor tissues Through thisstrategy nine types of cancer were successfully verified withenough specificity and sensitivity

34 Therapeutic Applications As described above nano-zymes have been widely used for detection and diagnos-tic methods Besides these applications many researchershave also studied therapeutic applications including anti-inflammatory effects neuroprotection stem cell growth andantiaging In general SOD was often utilized for therapeuticapplications owing to its protective role as a scavenger of reac-tive oxygen intermediates (ROIs) Intracellular concentrationof ROI including hydrogen peroxidase hypochlorite ionshydroxyl radicals hydroxyl ions and superoxide anions hasbeen known to be a cause of cell degeneration and associateddiseases [71] Inspired by earlier studies by Seal et al whichrevealed the activity of CeO

2NPs as a SOD-mimic [72 73]

various studies have been attempted to develop SOD-mimicking nanozymes

Chen at al reported that nanoceria as a SOD-mimicprevented retinal degeneration by inhibiting the productionof ROIs [74] In their work nanoceria prevented ROI-induced apoptosis and intracellular accumulation of ROIin cultured retinal neurons in the presence of H

2O2 They

further demonstrated that nanoceria injected into the eyes ofrats protected retina photoreceptor cells from light-induceddegeneration The study by Hirst et al also demonstratedthat nanoceria could be used for anti-inflammation byelimination of the radical oxygen species in J774A1 murinemacrophage cells [75]

Superparamagnetic iron oxide (SPIO) nanoparticles havebeen employed to promote growth of stem cells Huanget al reported that Ferucarbotran a commercialized SPIOcould promote cell growth in humanmesenchymal stem cells(hMSCs) by diminishing intracellular H

2O2and also accel-

erate cell cycle progression [76] In this report the intrinsicperoxidase-like activity of SPIO dramatically reduced intra-cellular H

2O2after internalization into hMSCs as well as

free iron ions released from lysosomal degradation of SPIO-affected cell cycle control molecules

35 Environmental Engineering Recently environmentalproblems such as water and air pollution food safety and

public health have become growing concerns in societyIn addition to the aforementioned applications nanozyme-based techniques have been explored for use in the field ofenvironmental technology

351 Pollutant Detection Ding et al developed a simpleand rapid colorimetric method for detecting melamine anorganic nitrogenous compound which is toxic when swal-lowed and has been illegally added to dairy products [77]The principle of this method is as follows Melamine inhibitsthe catalytic oxidation of colorimetric substrates (ABTS) byMNPs in the presence of H

2O2 because it competitively

reacts with H2O2 forming an additional compound Conse-

quently the intensity of the ABTS color signal was dependenton the concentration of melamine On the basis of thisreaction a colorimetric systemusingMNPs could enable easydetection by the naked eye of concentrations of melamineabove safety limits in dairy products

Nanocomposite-entrapping MNPs and oxidase in meso-porous carbonwere used to detect several phenol compoundsamperometrically such as phenol cresol and cathechol[49] These phenol compounds produced a concentration-dependent increase of cathodic current in this system whichmay have great potential in the field of environmentalmonitoring

352 Pollutant Removal Although there have been manymethods for removal of industrial dyestuffs such as absorp-tion precipitation and ultrasonic decomposition they couldnot efficiently degrade organic pollutants in wastewaterNanozyme-based methods have been found to be a power-ful cost-effective and simple method for degradation andmineralization of organic dyes from industrial processesMost prominently MNPs such as peroxidase have beeninvestigated for degradation of organic pollutants such asmethylene blue phenol and rhodamine B A MNP-baseddegradation method offers distinct advantages over existingdegradation methods which use HRP such as lower costhigh stability and reusability MNPs-H

2O2could remove

85 of phenol from aqueous solution within three hours[78] The MNPs-based degradation showed higher efficiencycompared to HRP-based degradation and stability in a broadrange of temperatures (5ndash90∘C) leading to ease of storageFurthermore MNPs could be captured by the application ofan external field and recycled for five rounds retaining almost100 of their activity Removal of methylene blue by MNPs-H2O2coupled method has also been successfully performed

by Jiang et al [79] It was observed that 96ofmethylene bluewas degraded in 15 minutes at optimized condition

Gao et al reported that MNPs-H2O2system could

degrade biofilm and kill resident bacteria [80] Biofilm espe-cially formed by Pseudomonas aeruginosa occurs in hospitalwater systems and medical devices with high frequencybecoming a common cause of nosocomial infection [81]In this report MNPs-H

2O2system exhibited significantly

higher efficiency than the use of H2O2in degradation of

biofilm The authors confirmed that additional free hydroxylradicals generated by MNP catalysis of H

2O2facilitated

the oxidative cleavage of biofilm components (nucleic acids

Journal of Nanomaterials 7

Table1Va

rious

applicationstu

dies

basedon

nano

zymes

Applicationfield

Nanozym

esAc

tivity

Detectio

nmetho

dDetails

Ref

Biosensor

MNPs

Peroxidase

Colorim

etric

H2O2biosensor

[9]

AuNPs

Glucose

oxidase

Colorim

etric

Nucleicacid

detection

[15]

Carboxyl-m

odified

graphene

oxide

Peroxidase

Colorim

etric

H2O2andglucoseb

iosensor

[23]

MNPs

Peroxidase

Colorim

etric

H2O2andglucoseb

iosensor

[44]

MNPs

Peroxidase

Colorim

etric

H2O2biosensor

[45]

MNPs

Peroxidase

Colorim

etric

H2O2biosensor

[46]

AuNPs

Peroxidase

Colorim

etric

H2O2andglucoseb

iosensor

[47]

MNPs

Peroxidase

Electro

chem

ical

Glucose

biosensor

[48]

MNPs

(with

oxidaseinmesop

orou

scarbo

n)Peroxidase

Electro

chem

ical

Glucose

biosensor

[49]

MNPs

(with

oxidaseinmesop

orou

ssilica)

Peroxidase

Colorim

etric

Glucose

andcholesterolbiosensor

[50]

MNPs

(with

oxidaseinmesop

orou

ssilica)

Peroxidase

Colorim

etric

Galactose

biosensor

[51]

MNPs

(with

oxidaseinmesop

orou

ssilica)

Peroxidase

Colorim

etric

Alcoh

olbiosensor

[52]

MNPs

Peroxidase

Colorim

etric

Nucleicacid

detection(Chlam

ydiatra

chom

atis)

[53]

CeO2NPs

Oxidase

Colorim

etric

Nucleicacid

detection(Chlam

ydiatra

chom

atis)

[56]

Chito

san-mod

ified

MNPs

with

thrombinaptamers

Peroxidase

Colorim

etric

Thrombindetection

[57]

Immun

oassay

MNPs

Peroxidase

Colorim

etric

Cardiactropo

ninI(Tn

I)detection

[9]

MNPs-PtN

Psin

mesop

orou

scarbo

nPeroxidase

Colorim

etric

Rotavirusa

ndHER

2detection

[33]

Graph

eneo

xide

Peroxidase

Colorim

etric

Prostatespecifica

ntigen

(PSA

)detectio

n[41]

Chito

san-mod

ified

MNPs

Peroxidase

Colorim

etric

Mou

seIgGandcarcinoembryonica

ntigen

detection

[63]

Prussia

nblue

mod

ified120574-Fe 2O3NPs

Peroxidase

Colorim

etric

IgGdetection

[64]

Ferritins

Peroxidase

Fluo

rometric

Avidin

andhu

man

ceruloplasmin

detection

[65]

MNPs

Peroxidase

Colorim

etric

Rotavirusa

ndHER

2detection

[66]

MNPs-PtN

Pson

graphene

oxide

Peroxidase

Colorim

etric

fluo

rometric

HER

2detectionandim

aging

[35]

Cancer

diagno

stics

(with

outimmun

ereactio

n)andtherapy

Poly(acrylicacid)-coated

CeO2NPs

Oxidase

Colorim

etric

Lung

cancer

celldetection

[13]

Poly(acrylicacid)-coated

CeO2NPs

Oxidase

Colorim

etric

Lung

andbreastcancer

celldetection

[69]

MagnetoferritinNPs

Peroxidase

Colorim

etric

fluo

rometric

Cancer

cellim

aging

[70]

CeO2NPs

Superoxide

dism

utase

Preventio

nof

retin

aldegeneratio

n[74]

CeO2NPs

Superoxide

dism

utase

Anti-infl

ammation

[75]

Superparam

agnetic

ironoxideN

PsPeroxidase

Prom

otionof

stem

cellgrow

th[76]

Environm

ental

engineering

MNPs

(with

oxidaseinmesop

orou

scarbo

n)Peroxidase

Electro

chem

ical

Phenolcresolandcathecho

ldetectio

n[49]

MNPs

Peroxidase

Colorim

etric

Mela

mined

etectio

n[77]

MNPs

Peroxidase

Removalof

phenol

[78]

MNPs

Peroxidase

Removalof

methylene

blue

[79]

MNPs

Peroxidase

Biofi

lmdegradation

[80]

8 Journal of Nanomaterials

proteins and polysaccharides) as well as killing residentbacteria

4 Conclusions and Future Research Aspects

Nanozymes have recently emerged as a potent alternativeto natural enzymes As discussed above although they arestill in the initial stages of research their use has developedsubstantially inmanydifferent detection and treatmentmeth-ods for biomolecules (Table 1) Despite the advantages ofnanozymes such as their low cost high stability robustnessease of mass production and long-term storability thereare several challenges to be tackled for practical use Firstlymost nanozymes have low activity compared to naturalenzymes Even if the nanomaterial itself is highly activeadditional coating and surface modification can decrease itsperformance Therefore development of novel nanozymesexhibiting high activity and appropriate surface-modificationtechniques are the emerging issues in the field of nanozymesNanozymes also have low selectivity to targets owing to theabsence of active sites where a substrate molecule binds andundergoes a chemical reaction in a natural enzyme Althoughresearchers have designed various types of surface-modifiednanozymes with polymers nucleic acids and antibodiesto provide selectivity mimicking natural enzymes this isstill insufficient for use in practical applications Toxicity ofnanozymes to humans and the ecosystem is also an essentialissue to be solved in regard to environmental and therapeuticapplications

In order for nanozymes to be positioned as a novelsource technology by efficiently overcoming the limitationsof natural enzymes we offer the following suggestions Thedevelopment of new nanozymes with higher activity andother positive properties than existing nanozymes is requiredWhile traditional research on developing nanozymes hasbeen performed by random screening of the enzyme-like activities of existing unspecified nanomaterials futureresearch will follow a strategy of rational screening ofenzyme-like activity based on those atomic compositionswhich are envisaged to catalyze enzymatic reactions Fur-thermore a strategy to prepare composites can be expectedto resolve the current major limitations of nanozymes oflow catalytic activity by exploiting their synergistic effectto facilitate electron transfer between composite materialsduring redox reaction Bioinspired synthesis of nanozymesalso provides an option to prepare nontoxic nanozymesby effectively circumventing the use of toxic chemicals inconventional chemical synthesis thereby accelerating theiruse in therapeutic applications Finally the developmentof novel surface engineering technology that can makenanozymes selective to target substrates will be importantin this field With the abovementioned research projects weexpect nanozymes to be widely employed in a wide range ofapplications in the near future

Conflict of Interests

The authors declare no financial or commercial conflict ofinterests

Acknowledgments

This work was supported by the Basic Science ResearchProgram through theNational Research Foundation of Korea(NRF) funded by the Ministry of Science ICT amp FuturePlanning (NRF-2014R1A1A1006016) and by the Gachon Uni-versity research fund of 2014 (GCU-2014-0110)

References

[1] D L Nelson and M M Cox Lehninger Principles of Biochem-istry vol 6 chapter 6 W H Freeman New York NY USA2005

[2] Z Liu R Cai L Mao H Huang and W Ma ldquoHighly sensitivespectrofluorimetric determination of hydrogen peroxide with120573-cyclodextrin-hemin as catalystrdquo Analyst vol 124 no 2 pp173ndash176 1999

[3] R P Bonar-Law and J K M Sanders ldquoPolyol recognition bya steroid-capped porphyrin Enhancement and modulation ofmisfit guest binding by added water or methanolrdquo Journal of theAmerican Chemical Society vol 117 no 1 pp 259ndash271 1995

[4] X-M Huang M Zhu L-Y Mao and H-X Shen ldquoCat-alytic determination of hydrogen peroxide by using themolybdenum-porphyrin complex as a mimetic enzyme ofperoxidaserdquo Analytical Sciences vol 13 no 1 pp 145ndash147 1997

[5] L Fruk andCMNiemeyer ldquoCovalent hemin-DNAadducts forgenerating a novel class of artificial heme enzymesrdquoAngewandteChemiemdashInternational Edition vol 44 no 17 pp 2603ndash26062005

[6] Q Wang Z Yang X Zhang X Xiao C K Chang and B XuldquoA supramolecular-hydrogel-encapsulated hemin as an artifi-cial enzyme to mimic peroxidaserdquo Angewandte Chemie Inter-national Edition vol 46 no 23 pp 4285ndash4289 2007

[7] Z Genfa and P K Dasgupta ldquoHematin as a peroxidase sub-stitute in hydrogen peroxide determinationsrdquo Analytical Chem-istry vol 64 no 5 pp 517ndash522 1992

[8] H Wei and E Wang ldquoNanomaterials with enzyme-like char-acteristics (nanozymes) next-generation artificial enzymesrdquoChemical Society Reviews vol 42 no 14 pp 6060ndash6093 2013

[9] L Gao J Zhuang LNie et al ldquoIntrinsic peroxidase-like activityof ferromagnetic nanoparticlesrdquo Nature Nanotechnology vol 2no 9 pp 577ndash583 2007

[10] R Polsky R Gill L Kaganovsky and I Willner ldquoNucleic acid-functionalized Pt nanoparticles catalytic labels for the ampli-fied electrochemical detection of biomoleculesrdquo AnalyticalChemistry vol 78 no 7 pp 2268ndash2271 2006

[11] T Li Y Du and E Wang ldquoPolyethyleneimine-functionalizedplatinum nanoparticles with high electrochemiluminescenceactivity and their applications to amplified analysis of bio-moleculesrdquo ChemistrymdashAn Asian Journal vol 3 no 11 pp1942ndash1948 2008

[12] W W He Y Liu J S Yuan et al ldquoAuPt nanostructures asoxidase and peroxidase mimetics for use in immunoassaysrdquoBiomaterials vol 32 no 4 pp 1139ndash1147 2011

[13] A Asati S Santra C Kaittanis S Nath and J M PerezldquoOxidase-like activity of polymer-coated cerium oxide nano-partielesrdquo Angewandte ChemiemdashInternational Edition vol 48no 13 pp 2308ndash2312 2009

[14] W J Luo C F Zhu S Su et al ldquoSelf-catalyzed self-limitinggrowth of glucose oxidase-mimicking gold nanoparticlesrdquo ACSNano vol 4 no 12 pp 7451ndash7458 2010

Journal of Nanomaterials 9

[15] X Zheng Q Liu C Jing et al ldquoCatalytic gold nanoparticles fornanoplasmonic detection of DNA hybridizationrdquo AngewandteChemie International Edition vol 50 no 50 pp 11994ndash119982011

[16] Y J Long Y F Li Y Liu J J Zheng J Tang and C JHuang ldquoVisual observation of the mercury-stimulated peroxi-dase mimetic activity of gold nanoparticlesrdquo Chemical Commu-nications vol 47 no 43 pp 11939ndash11941 2011

[17] W Chen J Chen Y-B Feng et al ldquoPeroxidase-like activityof water-soluble cupric oxide nanoparticles and its analyticalapplication for detection of hydrogen peroxide and glucoserdquoAnalyst vol 137 no 7 pp 1706ndash1712 2012

[18] W Luo Y-S Li J Yuan et al ldquoUltrasensitive fluorometricdetermination of hydrogen peroxide and glucose by usingmultiferroic BiFeO

3nanoparticles as a catalystrdquo Talanta vol 81

no 3 pp 901ndash907 2010[19] S H He W B Shi X D Zhang J A Li and Y M Huang ldquo120573-

Cyclodextrins-based inclusion complexes of CoFe2O4magnetic

nanoparticles as catalyst for the luminol chemiluminescencesystem and their applications in hydrogen peroxide detectionrdquoTalanta vol 82 no 1 pp 377ndash383 2010

[20] W B Shi X D Zhang S H He and Y M Huang ldquoCoFe2O4

magnetic nanoparticles as a peroxidasemimicmediated chemi-luminescence for hydrogen peroxide and glucoserdquo ChemicalCommunications vol 47 no 38 pp 10785ndash10787 2011

[21] Y W Fan and Y M Huang ldquoThe effective peroxidase-likeactivity of chitosan-functionalized CoFe

2O4nanoparticles for

chemiluminescence sensing of hydrogen peroxide and glucoserdquoAnalyst vol 137 no 5 pp 1225ndash1231 2012

[22] A K Dutta S K Maji D N Srivastava et al ldquoSynthesis ofFeS and FeSe nanoparticles from a single source precursor astudy of their photocatalytic activity peroxidase-like behaviorand electrochemical sensing of H

2O2rdquo ACS Applied Materials

and Interfaces vol 4 no 4 pp 1919ndash1927 2012[23] Y Song K Qu C Zhao J Ren and X Qu ldquoGraphene oxide

intrinsic peroxidase catalytic activity and its application toglucose detectionrdquoAdvancedMaterials vol 22 no 19 pp 2206ndash2210 2010

[24] Y Song X Wang C Zhao K Qu J Ren and X Qu ldquoLabel-free colorimetric detection of single nucleotide polymorphismby using single-walled carbon nanotube intrinsic peroxidase-like activityrdquo ChemistrymdashA European Journal vol 16 no 12 pp3617ndash3621 2010

[25] Y Guo J Li and S Dong ldquoHemin functionalized graphenenanosheets-based dual biosensor platforms for hydrogen per-oxide and glucoserdquo Sensors and Actuators B Chemical vol 160no 1 pp 295ndash300 2011

[26] J Xie X Zhang H Wang H Zheng Y Huang and J XieldquoAnalytical and environmental applications of nanoparticles asenzyme mimeticsrdquo TrACmdashTrends in Analytical Chemistry vol39 pp 114ndash129 2012

[27] A K Gupta and M Gupta ldquoSynthesis and surface engineeringof iron oxide nanoparticles for biomedical applicationsrdquoBioma-terials vol 26 no 18 pp 3995ndash4021 2005

[28] J Mu Y Wang M Zhao and L Zhang ldquoIntrinsic peroxidase-like activity and catalase-like activity of Co

3O4nanoparticlesrdquo

Chemical Communications vol 48 no 19 pp 2540ndash2542 2012[29] Y Wan P Qi D Zhang J Wu and Y Wang ldquoMan-

ganese oxide nanowire-mediated enzyme-linked immunosor-bent assayrdquo Biosensors and Bioelectronics vol 33 no 1 pp 69ndash74 2012

[30] R Andre F Natalio M Humanes et al ldquoV2O5nanowires

with an intrinsic peroxidase-like activityrdquo Advanced FunctionalMaterials vol 21 no 3 pp 501ndash509 2011

[31] W Chen J Chen A-L Liu L-M Wang G-W Li and X-H Lin ldquoPeroxidase-like activity of cupric oxide nanoparticlerdquoChemCatChem vol 3 no 7 pp 1151ndash1154 2011

[32] Y-L DongH-G Zhang Z U Rahman et al ldquoGraphene oxide-Fe3O4magnetic nanocomposites with peroxidase-like activity

for colorimetric detection of glucoserdquo Nanoscale vol 4 no 13pp 3969ndash3976 2012

[33] M I Kim Y Ye M-A Woo J Lee and H G Park ldquoA highlyefficient colorimetric immunoassay using a nanocompositeentrapping magnetic and platinum nanoparticles in orderedmesoporous carbonrdquo Advanced Healthcare Materials vol 3 no1 pp 36ndash41 2014

[34] J Liu X Hu S Hou et al ldquoAuPt coreshell nanorods withperoxidase- and ascorbate oxidase-like activities for improveddetection of glucoserdquo Sensors and Actuators B Chemical vol166-167 pp 708ndash714 2012

[35] M I Kim M S Kim M-AWoo et al ldquoHighly efficient colori-metric detection of target cancer cells utilizing superior catalyticactivity of graphene oxide-magnetic-platinum nanohybridsrdquoNanoscale vol 6 no 3 pp 1529ndash1536 2014

[36] M Liu H Zhao S Chen H Yu and X Quan ldquoInterface engi-neering catalytic graphene for smart colorimetric biosensingrdquoACS Nano vol 6 no 4 pp 3142ndash3151 2012

[37] Y Ye T Kong X Yu YWu K Zhang and XWang ldquoEnhancednonenzymatic hydrogen peroxide sensing with reducedgraphene oxideferroferric oxide nanocompositesrdquo Talantavol 89 pp 417ndash421 2012

[38] R Cui Z Han and J-J Zhu ldquoHelical carbon nanotubesintrinsic peroxidase catalytic activity and its application forbiocatalysis and biosensingrdquo ChemistrymdashA European Journalvol 17 no 34 pp 9377ndash9384 2011

[39] M Liu H Zhao S Chen H Yu and X Quan ldquoStimuli-responsive peroxidase mimicking at a smart graphene inter-facerdquo Chemical Communications vol 48 no 56 pp 7055ndash70572012

[40] S Liu J Tian L Wang Y Luo and X Sun ldquoA general strategyfor the production of photoluminescent carbon nitride dotsfrom organic amines and their application as novel peroxidase-like catalysts for colorimetric detection of H

2O2and glucoserdquo

RSC Advances vol 2 no 2 pp 411ndash413 2012[41] F Qu T Li and M Yang ldquoColorimetric platform for visual

detection of cancer biomarker based on intrinsic peroxidaseactivity of graphene oxiderdquo Biosensors and Bioelectronics vol26 no 9 pp 3927ndash3931 2011

[42] W Shi QWang Y Long et al ldquoCarbon nanodots as peroxidasemimetics and their applications to glucose detectionrdquo ChemicalCommunications vol 47 no 23 pp 6695ndash6697 2011

[43] X Wang K Qu B Xu J Ren and X Qu ldquoMulticolorluminescent carbon nanoparticles synthesis supramolecularassembly with porphyrin intrinsic peroxidase-like catalyticactivity and applicationsrdquo Nano Research vol 4 no 9 pp 908ndash920 2011

[44] H Wei and E Wang ldquoFe3O4magnetic nanoparticles as per-

oxidase mimetics and their applications in H2O2and glucose

detectionrdquo Analytical Chemistry vol 80 no 6 pp 2250ndash22542008

[45] Q Chang KDeng L ZhuG Jiang C Yu andH Tang ldquoDeter-mination of hydrogen peroxide with the aid of peroxidase-like

10 Journal of Nanomaterials

Fe3O4magnetic nanoparticles as the catalystrdquo Microchimica

Acta vol 165 no 3-4 pp 299ndash305 2009[46] Z Jiang L Kun H Ouyang A Liang and H Jiang ldquoA simple

and sensitive fluorescence quenching method for the determi-nation of H

2O2using rhodamine B and Fe

3O4nanocatalystrdquo

Journal of Fluorescence vol 21 no 5 pp 2015ndash2020 2011[47] Y Jv B Li andR Cao ldquoPositively-charged gold nanoparticles as

peroxidiase mimic and their application in hydrogen peroxideand glucose detectionrdquo Chemical Communications vol 46 no42 pp 8017ndash8019 2010

[48] K Wang J-J Xu D-C Sun H Wei and X-H Xia ldquoSelectiveglucose detection based on the concept of electrochemicaldepletion of electroactive species in diffusion layerrdquo Biosensorsand Bioelectronics vol 20 no 7 pp 1366ndash1372 2005

[49] M I Kim Y Ye B Y Won S Shin J Lee and H G Park ldquoAhighly efficient electrochemical biosensing platform by employ-ing conductive nanocomposite entrapping magnetic nano-particles and oxidase in mesoporous carbon foamrdquo AdvancedFunctional Materials vol 21 no 15 pp 2868ndash2875 2011

[50] M I Kim J Shim T Li J Lee and H G Park ldquoFabrica-tion of nanoporous nanocomposites entrapping Fe

3O4mag-

netic nanoparticles and oxidases for colorimetric biosensingrdquoChemistrymdashAEuropean Journal vol 17 no 38 pp 10700ndash107072011

[51] M I Kim J Shim T Li et al ldquoColorimetric quantificationof galactose using a nanostructured multi-catalyst systementrapping galactose oxidase and magnetic nanoparticles asperoxidasemimeticsrdquoAnalyst vol 137 no 5 pp 1137ndash1143 2012

[52] M I Kim J Shim H J Parab S C Shin J Lee and H G ParkldquoA convenient alcohol sensor using one-pot nanocompositeentrapping alcohol oxidase and magnetic nanoparticles as per-oxidase mimeticsrdquo Journal of Nanoscience and Nanotechnologyvol 12 no 7 pp 5914ndash5919 2012

[53] K S Park M I Kim D-Y Cho and H G Park ldquoLabel-free colorimetric detection of nucleic acids based on target-induced shielding against the peroxidase-mimicking activity ofmagnetic nanoparticlesrdquo Small vol 7 no 11 pp 1521ndash1525 2011

[54] J A Brinkman M Z Rahmani W E Jones A K Chaturvediand M E Hagensee ldquoOptimization of PCR based detection ofhuman papillomavirus DNA from urine specimensrdquo Journal ofClinical Virology vol 29 no 4 pp 230ndash240 2004

[55] L Hafner K Beagley and P Timms ldquoChlamydia trachomatisinfection host immune responses and potential vaccinesrdquoMucosal Immunology vol 1 no 2 pp 116ndash130 2008

[56] M I Kim K S Park and H G Park ldquoUltrafast colorimetricdetection of nucleic acids based on the inhibition of the oxidaseactivity of cerium oxide nanoparticlesrdquo Chemical Communica-tions vol 50 no 67 pp 9577ndash9580 2014

[57] Z Zhang Z Wang X Wang and X Yang ldquoMagneticnanoparticle-linked colorimetric aptasensor for the detection ofthrombinrdquo Sensors and Actuators B Chemical vol 147 no 2 pp428ndash433 2010

[58] B W Blais and A Martinez-Perez ldquoDetection of groupD salmonellae including Salmonella enteritidis in eggs bypolymyxin-based enzyme-linked immunosorbent assayrdquo Jour-nal of Food Protection vol 71 no 2 pp 392ndash396 2008

[59] V Tripathi S Nara S K Chaube et al ldquoDevelopment ofrapid and sensitive one-step direct enzyme linked immunosor-bent assay for 17-120572-OH-progesterone in serumrdquo Journal ofImmunoassay and Immunochemistry vol 29 no 2 pp 117ndash1272008

[60] K DMcReynolds M J Hadd and J Gervay-Hague ldquoSynthesisof biotinylated glycoconjugates and their use in a novel ELISAfor direct comparison ofHIV-1 gp120 recognition ofGalCer andrelated carbohydrate analoguesrdquo Bioconjugate Chemistry vol10 no 6 pp 1021ndash1031 1999

[61] H Hocini S Iscaki J-P Bouvet M D Kazatchkine and LBelec ldquoAn ELISA method to measure total and specific humansecretory IgA subclasses based on selective degradation by IgA1-proteaserdquo Journal of Immunological Methods vol 235 no 1-2pp 53ndash60 2000

[62] L Micheli S Di Stefano D Moscone et al ldquoProduction ofantibodies and development of highly sensitive formats ofenzyme immunoassay for saxitoxin analysisrdquo Analytical andBioanalytical Chemistry vol 373 no 8 pp 678ndash684 2002

[63] L Gao J Wu S Lyle K Zehr L Cao and D Gao ldquoMagnetitenanoparticle-linked immunosorbent assayrdquo Journal of PhysicalChemistry C vol 112 no 44 pp 17357ndash17361 2008

[64] X-Q Zhang S-W Gong Y Zhang T Yang C-YWang andNGu ldquoPrussian blue modified iron oxide magnetic nanoparticlesand their high peroxidase-like activityrdquo Journal of MaterialsChemistry vol 20 no 24 pp 5110ndash5116 2010

[65] Z Tang H Wu Y Zhang Z Li and Y Lin ldquoEnzyme-mimicactivity of ferric nano-core residing in ferritin and its biosensingapplicationsrdquo Analytical Chemistry vol 83 no 22 pp 8611ndash8616 2011

[66] M-A Woo M I Kim J H Jung K S Park T S Seoand H G Park ldquoA novel colorimetric immunoassay utilizingthe peroxidase mimicking activity of magnetic nanoparticlesrdquoInternational Journal of Molecular Sciences vol 14 no 5 pp9999ndash10014 2013

[67] V H C Bramwell G S Doig A B Tuck et al ldquoChangesover time of extracellular domain of HER2 (ECDHER2) serumlevels have prognostic value in metastatic breast cancerrdquo BreastCancer Research andTreatment vol 114 no 3 pp 503ndash511 2009

[68] K S Asgeirsson A Agrawal C Allen et al ldquoSerum epidermalgrowth factor receptor and HER2 expression in primary andmetastatic breast cancer patientsrdquo Breast Cancer Research vol9 no 6 article R75 2007

[69] A Asati C Kaittanis S Santra and J M Perez ldquoPH-tunableoxidase-like activity of cerium oxide nanoparticles achievingsensitive fluorigenic detection of cancer biomarkers at neutralpHrdquo Analytical Chemistry vol 83 no 7 pp 2547ndash2553 2011

[70] K L Fan C Q Cao Y X Pan et al ldquoMagnetoferritinnanoparticles for targeting and visualizing tumour tissuesrdquoNature Nanotechnology vol 7 no 7 pp 459ndash464 2012

[71] S Beatty H-H Koh M Phil D Henson and M BoultonldquoThe role of oxidative stress in the pathogenesis of age-relatedmacular degenerationrdquo Survey of Ophthalmology vol 45 no 2pp 115ndash134 2000

[72] C Korsvik S Patil S Seal and W T Self ldquoSuperoxidedismutase mimetic properties exhibited by vacancy engineeredceria nanoparticlesrdquo Chemical Communications no 10 pp1056ndash1058 2007

[73] E G Heckert A S Karakoti S Seal andW T Self ldquoThe role ofcerium redox state in the SOD mimetic activity of nanoceriardquoBiomaterials vol 29 no 18 pp 2705ndash2709 2008

[74] J Chen S Patil S Seal and J F McGinnis ldquoRare earthnanoparticles prevent retinal degeneration induced by intracel-lular peroxidesrdquo Nature Nanotechnology vol 1 no 2 pp 142ndash150 2006

Journal of Nanomaterials 11

[75] S M Hirst A S Karakoti R D Tyler N Sriranganathan SSeal and C M Reilly ldquoAnti-inflammatory properties of ceriumoxide nanoparticlesrdquo Small vol 5 no 24 pp 2848ndash2856 2009

[76] D-M Huang J-K Hsiao Y-C Chen et al ldquoThe promotion ofhuman mesenchymal stem cell proliferation by superparamag-netic iron oxide nanoparticlesrdquo Biomaterials vol 30 no 22 pp3645ndash3651 2009

[77] N Ding N Yan C Ren and X Chen ldquoColorimetric determi-nation of melamine in dairy products by Fe

3O4Magnetic nano-

particles-H2O2-ABTS detection systemrdquo Analytical Chemistry

vol 82 no 13 pp 5897ndash5899 2010[78] J Zhang J Zhuang L Gao et al ldquoDecomposing phenol by the

hidden talent of ferromagnetic nanoparticlesrdquo Chemospherevol 73 no 9 pp 1524ndash1528 2008

[79] J Z Jiang J Zou L H Zhu L Huang H Jiang and YZhang ldquoDegradation of methylene blue with H

2O2activated

by peroxidase-like Fe3O4magnetic nanoparticlesrdquo Journal of

Nanoscience and Nanotechnology vol 11 no 6 pp 4793ndash47992011

[80] L Gao K M Giglio J L Nelson H Sondermann and AJ Travis ldquoFerromagnetic nanoparticles with peroxidase-likeactivity enhance the cleavage of biological macromolecules forbiofilm eliminationrdquo Nanoscale vol 6 no 5 pp 2588ndash25932014

[81] K Vickery A Pajkos and Y Cossart ldquoRemoval of biofilmfrom endoscopes evaluation of detergent efficiencyrdquo AmericanJournal of Infection Control vol 32 no 3 pp 170ndash176 2004

Submit your manuscripts athttpwwwhindawicom

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CorrosionInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Polymer ScienceInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CeramicsJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CompositesJournal of

NanoparticlesJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

Biomaterials

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NanoscienceJournal of

TextilesHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Journal of

NanotechnologyHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

CrystallographyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

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CoatingsJournal of

Advances in

Materials Science and EngineeringHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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MetallurgyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

MaterialsJournal of

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Nano

materials

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal ofNanomaterials

Page 4: Review Article Recent Research Trends and Future …downloads.hindawi.com/journals/jnm/2015/756278.pdfnovel biosensor, immunoassay, cancer diagnostics, therapeutics, and environmental

4 Journal of Nanomaterials

in the construction of glucose biosensors Wang et al devel-oped a colorimetric glucose detection platform by combiningthe catalytic oxidation of glucose with GOx and the catalyticreaction of ABTS withMNPs [48] Glucose concentrations aslow as 30 120583M were detected with a linear range from 50 120583Mto 1mM in this study

There have been several reports of an electrochemi-cal biosensing platform using GOx-coupled nanozymes Ahighly efficient and robust electrochemical biosensing strat-egy employing a nanocomposite harboring GOx-couplednanozymes was developed by our group [49] In this reportMNPs and GOx were entrapped in the pores of mesoporouscarbon in which GOx immobilized in the nanocompositegenerates H

2O2which then is directly reduced to H

2O

with the electrocatalytic reduction mediated by MNPs Thissystem showed a linear range of (05 to 10) times 10minus3M and adetection limit of 02 times 10minus3M

313 Oxidase-Coupled Methods (Except Glucose Oxidase)On the basis of the mechanism of glucose detection aboveseveral different oxidases have also been coupled withnanozymes for the fabrication of biosensing platforms Ananostructured multicatalyst system consisting of MNPsand cholesterol oxidase entrapped in large-pore-sized meso-porous silica has been developed for convenient colorimetricdetection of cholesterol [50] This multicatalyst system iscomposed of MNPs incorporated in the wall of mesocellularsilica pores forming magnetic mesoporous silica (MMS)and cholesterol oxidases In this system cholesterol oxidaseimmobilized in the MMS promotes a reaction with choles-terol to generate H

2O2 which subsequently activates MNPs

in the mesocellular silica pores to convert a colorimetric sub-strate into a colored product The result of this investigationshows the cholesterol oxidase-coupled method to have highselectivity and sensitivity (limit of detection LOD of 5120583Min the linear range from 10 to 250 120583M) for the detection ofcholesterol A colorimetricmethod for detection of galactosewhich utilizes a nanostructured multicatalyst system consist-ing of MNPs and galactose oxidase has also been reported[51] The clinical applicability of this multicatalytic systemwas successfully evaluated as a promising analytical tool todiagnose galactosemia by determining the concentration ofgalactose eluted from the dried blood specimens provided byclinical hospitals

Apart from the above oxidases alcohol oxidase has beenused in a colorimetric biosensor for quantification of ethanoland methanol [52] The nanocomposite system utilizingalcohol oxidase entrapped in mesocellular silica with MNPsprovided a rapid and convenient platform for analysis ofalcohol with high stability and reusability It showed a linearconcentration range from 100 to 500120583M with a detectionlimit as low as 25 120583M

314 OtherMethods Recently peroxidase-mimicking nano-materials such as MNPs CeO

2NPs and Au NPs [15] have

been employed for new methods of DNA detection A label-free colorimetric detection method for nucleic acids hasbeen developed [53] In this method the target DNA inthe sample which is amplified by polymerase chain reaction

(PCR) is directly adsorbed on the surface of the MNPs dueto electrostatic interactions between the negatively chargedphosphate backbone and the positively charged surface of theNPs thereby inducing a shielding effect against colorimetricsubstrate binding to MNPs The peroxidase activity of MNPswill decrease due to the DNA-induced shielding so thatthe intensity of the color signal will also be significantlyreduced Using this detection method researchers succes-sively detectedChlamydia trachomatis in humanurine whichis one of the common bacteria causing sexually transmitteddisease (STD) [54 55] CeO

2NPs were also employed in a

label-free colorimetric method for detecting C trachomatisand this method provided ultrafast detection of the targetnucleic acid (target nucleic acids can be determined withina few minutes) [56]

A novel biosensing format using aptamers has been devel-oped by several researchers based on the fact that aptamerswhich are ssDNA or ssRNA that can specifically bind to atarget can replace antibodies for the specific recognition oftarget molecules A method using chitosan-modified MNPsconjugated with thrombin aptamers was reported by Zhangrsquosgroup [57] They constructed a sandwich-type assay for thedetection of thrombin with two thrombin aptamers Thisaptamer-based assay showed a linear detection range from 1to 100 nM and a detection limit of 1 nM of thrombin

32 Immunoassays Immunoassays have been used in hos-pitals laboratory medicine and research to improve thehealth and well-being of humans and animals Informationgained by clinical immunoassay testing has shortened thelength of hospital stays and decreased the severity of illnessby identifying and assessing the progression of diseasethereby leading to improved therapeutic choices In lifescience research immunoassays are used in the study ofbiological systems for tracking different proteins hormonesand antibodies In industry immunoassays are used to detectcontaminants in food and water and in quality control tomonitor specific molecules used during product processingHowever themost commonly used enzymes in immunoassayinclude horseradish peroxidase and alkaline phosphatase[58ndash62] which lose their enzymatic activities gradually overlong-term storage [63] To overcome these limits variousstudies on replacing natural enzymes have been reported andconsequently novel types of immunoassay using nanozymesin place of HRP have been developed

321 Sandwich or Antigen-Down Type Immunoassays Gaoand coworkers reported an immunoassay using chitosan-modified MNPs (CS-MNPs) as a replacement for HRP in thetraditional immunoassay [63] They provided protocols forantigen-down and sandwich immunoassays with CS-MNPsand detected mouse IgG and carcinoembryonic antigen(CEA) respectively Chitosan modified on the surface ofMNPs prevented aggregation of MNPs so that MNPs wereeasily dispersed in aqueous solutions Meanwhile aminogroups in the chitosan provided a convenient site for covalentlinking of antibodies to MNPs thereby replacing the linkageof HRP-conjugated antibodies to CS-MNP-conjugated anti-bodies in the immunoassay Capture-detection immunoassay

Journal of Nanomaterials 5

was also developed to detect CEA by employing themagneticproperties of CS-MNPs which facilitate capturing separat-ing and enriching antigens as well as redispersing the MNPaggregation in solution

Zhang and coworkers reported a novel immunoassayutilizing Prussian blue modified 120574-Fe

2O3NPs [64] Prus-

sian blue a dark blue pigment with the idealized formulaFe7(CN)18 was modified on the surface of 120574-Fe

2O3NPs due

to its excellent electrochemical behavior that accelerated elec-tron transfer and its catalytic properties that could catalyzethe reduction of H

2O2 Prussian blue modified 120574-Fe

2O3NPs

(PBMNPs) were next conjugated with staphylococcal proteinA (SPA) to bind to IgG immobilized in the well so thatPBMNPs could derive a colorimetric reaction in the presenceof TMB and H

2O2

Ferritins nanoscale globular protein cages encapsulatinga ferric core were used in immunoassay in Tang et alrsquos study[65] In this study ferritin showed a thermally stable and pH-tolerable enzyme-mimetic activity derived from the ferricnanocore of ferritin Two forms of immunoassay systemswere constructed antigen-down type and sandwich typeAvidin was selected as the target molecule of the antigen-down immunoassay and nitrated human ceruloplasmin asthe target molecule of the sandwich-type immunoassayTheyalso reported that the ferritins could be utilized in analyticalapplications such as H

2O2assay In their assay ferritin

oxidizes the p-HPPA in the presence of H2O2to generate

a fluorescent product This ferritin-based H2O2assay shows

a detection limit of 016 120583M and a linear detection range of40 120583M which is one-order higher sensitivity with a broaderlinear response range

Immunoassay systems for detection of rotavirus andbreast cancer have been developed [66] in which MNPsare conjugated to antibodies against rotaviruses and humanepidermal growth factor receptor 2 (HER2) In this sys-tem sandwich-type and antigen-down type immunoassaywere used to detect rotavirus and HER2 respectively Forthe detection of rotavirus rotavirus antibodies were firstimmobilized in a well and rotavirus bound to the immo-bilized antibody Subsequently MNP-conjugated antibodies(MNP-Abs) were added to the well in order to bind tocaptured rotaviruses Finally the peroxidase substrate TMBwas changed into blue-colored products in the presence ofH2O2 An antigen-down immunoassay system was used in

the case of breast cell detection which did not require priorimmobilization of antibodies in the bare well surface Breastcells were cultured in a well so that they adsorbed to thesurface of the well MNPs-Abs were then applied to the cell-cultured well followed by adding TMB and H

2O2to induce

a colorimetric reactionThis assay system displayed excellentspecificity sensitivity and linearity for quantitative detectionof the target molecules as well as the production of a colorsignal that could be detected by the naked eye

Based on the above system a nanocomposite-basedimmunoassay was also performed in which nanocompositeentrappingMNPs and Pt NPs in ordered mesoporous carbon(OMC) were utilized instead of HRP [33]This immunoassaygenerated significantly higher absorption intensity of colorsignal than the current ELISA and was able to quantify the

target antigen very rapidly within three minutes while theconventional ELISA requires several tens of minutes for colorsignal development [67 68] It showed a limit of detection(LOD) for HER2 of 15 ngmLminus1 in the linear range from 25 to100 ngmLminus1 The nanocomposite was found to have 50 timeshigher catalytic efficiency than that of free MNPs owing tothe high catalytic action of Pt NPs

Graphene oxide (GO) has been used in immunoassay as aperoxidase-mimicking nanozyme [41] Yanrsquos group developeda sandwich-type immunoassay for the detection of cancerbiomarker prostate specific antigen (PSA) In this work amagnetic bead (MB) was used to immobilize the primaryPSA antibody (Ab

1) and then a GO-conjugated secondary

antibody (Ab2) was applied in the presence of PSA Subse-

quentlyMB-Ab1was separated from the immunocomplex by

an external magnetic field and GO catalyzed the oxidation ofhydroquinone in the presence of H

2O2to generate a brown-

colored productConjugating both MNPs and Pt NPs on the surface of

GO enabled highly sensitive and rapid colorimetric detectionof the target cancer cell [35] In this work it was notablethat the electron transfer between MNPs and Pt NPs createsa synergistic effect significantly enhancing the catalyticperformance of MNPs-Pt NPs-GO nanohybrids Using thisimmunoassay system human breast adenocarcinoma cells(SKBR-3) which overexpressed HER2 were detected in fiveminutes with high specificity and sensitivity The LOD fortarget SKBR-3 cells was found to be about 100 cells in thelinear range from 100 to 1000 cells Moreover fluorescenceimaging of SKBR-3 was successfully performed with MNPs-Pt NPs-GO nanohybrids

322 Other Immunoassays By employing the superparam-agnetic property of MNPs a capture-detection immunoassaysystem has been developed by Gaorsquos group [63] In the proce-dure the CS-MNPs were conjugated with carcinoembryonicantibodies (anti-CEA M111147) and then mixed with thesample containing CEA After the CEA was captured byMNPs a magnetic field was applied to separate the MNPswhich had captured CEA Finally the MNPs capturing CEAwere injected into microplate wells coated with anothermonoclonal CEA antibody creating the sandwich formatThereby the MNPs prompted the generation of a color signalupon addition of colorimetric substrate and H

2O2to the

wells Cardiac troponin I (TnI) in serum a well-knownbiomarker for myocardial infarction was also detected by acapture-detection immunoassay utilizing the magnetism andperoxidase ability of MNPs [9]

33 Cancer Diagnostics without Immune Reaction Asidefrom immunoassay using antigen-antibody interaction othernovel assays using nanozymes have been developed partic-ularly for the diagnosis of tumor cells Asati and coworkersreported an assay for the determination of tumor cellswith poly(acrylic acid)-coated CeO

2NPs (nanoceria) as an

oxidase mimic [13] When the nanoparticles were conjugatedwith folic acid they bound to folate receptors on the tumorcell (A-549 lung cancer cells) due to high expression offolate receptors on the tumor cell surface Polymer-coated

6 Journal of Nanomaterials

nanoceria as an oxidase mimic made detection of tumorcells easier than with traditional immunoassay because itdirectly oxidized a colorimetric substrate to a colored productwithout H

2O2and additional steps to introduce an enzyme-

conjugated secondary antibody Further advances in thistechnology were also reported by employing a fluorescence-generating substrate ampliflu to detect target cancer cells ataround neutral pH [69]

Another interesting study to visualize target tumor tissueswithout the use of any additional targeting ligands hasalso been described [70] In this study peroxidase-like ironoxide nanoparticles were encapsulated inside a recombinanthuman heavy-chain ferritin (Hfn) protein shell which bindsto tumor cells that overexpress transferrin receptor 1The ironoxide cores catalyzed the oxidation of peroxidase substratesin the presence of H

2O2to produce the colorimetric signal

that was used to visualize tumor tissues Through thisstrategy nine types of cancer were successfully verified withenough specificity and sensitivity

34 Therapeutic Applications As described above nano-zymes have been widely used for detection and diagnos-tic methods Besides these applications many researchershave also studied therapeutic applications including anti-inflammatory effects neuroprotection stem cell growth andantiaging In general SOD was often utilized for therapeuticapplications owing to its protective role as a scavenger of reac-tive oxygen intermediates (ROIs) Intracellular concentrationof ROI including hydrogen peroxidase hypochlorite ionshydroxyl radicals hydroxyl ions and superoxide anions hasbeen known to be a cause of cell degeneration and associateddiseases [71] Inspired by earlier studies by Seal et al whichrevealed the activity of CeO

2NPs as a SOD-mimic [72 73]

various studies have been attempted to develop SOD-mimicking nanozymes

Chen at al reported that nanoceria as a SOD-mimicprevented retinal degeneration by inhibiting the productionof ROIs [74] In their work nanoceria prevented ROI-induced apoptosis and intracellular accumulation of ROIin cultured retinal neurons in the presence of H

2O2 They

further demonstrated that nanoceria injected into the eyes ofrats protected retina photoreceptor cells from light-induceddegeneration The study by Hirst et al also demonstratedthat nanoceria could be used for anti-inflammation byelimination of the radical oxygen species in J774A1 murinemacrophage cells [75]

Superparamagnetic iron oxide (SPIO) nanoparticles havebeen employed to promote growth of stem cells Huanget al reported that Ferucarbotran a commercialized SPIOcould promote cell growth in humanmesenchymal stem cells(hMSCs) by diminishing intracellular H

2O2and also accel-

erate cell cycle progression [76] In this report the intrinsicperoxidase-like activity of SPIO dramatically reduced intra-cellular H

2O2after internalization into hMSCs as well as

free iron ions released from lysosomal degradation of SPIO-affected cell cycle control molecules

35 Environmental Engineering Recently environmentalproblems such as water and air pollution food safety and

public health have become growing concerns in societyIn addition to the aforementioned applications nanozyme-based techniques have been explored for use in the field ofenvironmental technology

351 Pollutant Detection Ding et al developed a simpleand rapid colorimetric method for detecting melamine anorganic nitrogenous compound which is toxic when swal-lowed and has been illegally added to dairy products [77]The principle of this method is as follows Melamine inhibitsthe catalytic oxidation of colorimetric substrates (ABTS) byMNPs in the presence of H

2O2 because it competitively

reacts with H2O2 forming an additional compound Conse-

quently the intensity of the ABTS color signal was dependenton the concentration of melamine On the basis of thisreaction a colorimetric systemusingMNPs could enable easydetection by the naked eye of concentrations of melamineabove safety limits in dairy products

Nanocomposite-entrapping MNPs and oxidase in meso-porous carbonwere used to detect several phenol compoundsamperometrically such as phenol cresol and cathechol[49] These phenol compounds produced a concentration-dependent increase of cathodic current in this system whichmay have great potential in the field of environmentalmonitoring

352 Pollutant Removal Although there have been manymethods for removal of industrial dyestuffs such as absorp-tion precipitation and ultrasonic decomposition they couldnot efficiently degrade organic pollutants in wastewaterNanozyme-based methods have been found to be a power-ful cost-effective and simple method for degradation andmineralization of organic dyes from industrial processesMost prominently MNPs such as peroxidase have beeninvestigated for degradation of organic pollutants such asmethylene blue phenol and rhodamine B A MNP-baseddegradation method offers distinct advantages over existingdegradation methods which use HRP such as lower costhigh stability and reusability MNPs-H

2O2could remove

85 of phenol from aqueous solution within three hours[78] The MNPs-based degradation showed higher efficiencycompared to HRP-based degradation and stability in a broadrange of temperatures (5ndash90∘C) leading to ease of storageFurthermore MNPs could be captured by the application ofan external field and recycled for five rounds retaining almost100 of their activity Removal of methylene blue by MNPs-H2O2coupled method has also been successfully performed

by Jiang et al [79] It was observed that 96ofmethylene bluewas degraded in 15 minutes at optimized condition

Gao et al reported that MNPs-H2O2system could

degrade biofilm and kill resident bacteria [80] Biofilm espe-cially formed by Pseudomonas aeruginosa occurs in hospitalwater systems and medical devices with high frequencybecoming a common cause of nosocomial infection [81]In this report MNPs-H

2O2system exhibited significantly

higher efficiency than the use of H2O2in degradation of

biofilm The authors confirmed that additional free hydroxylradicals generated by MNP catalysis of H

2O2facilitated

the oxidative cleavage of biofilm components (nucleic acids

Journal of Nanomaterials 7

Table1Va

rious

applicationstu

dies

basedon

nano

zymes

Applicationfield

Nanozym

esAc

tivity

Detectio

nmetho

dDetails

Ref

Biosensor

MNPs

Peroxidase

Colorim

etric

H2O2biosensor

[9]

AuNPs

Glucose

oxidase

Colorim

etric

Nucleicacid

detection

[15]

Carboxyl-m

odified

graphene

oxide

Peroxidase

Colorim

etric

H2O2andglucoseb

iosensor

[23]

MNPs

Peroxidase

Colorim

etric

H2O2andglucoseb

iosensor

[44]

MNPs

Peroxidase

Colorim

etric

H2O2biosensor

[45]

MNPs

Peroxidase

Colorim

etric

H2O2biosensor

[46]

AuNPs

Peroxidase

Colorim

etric

H2O2andglucoseb

iosensor

[47]

MNPs

Peroxidase

Electro

chem

ical

Glucose

biosensor

[48]

MNPs

(with

oxidaseinmesop

orou

scarbo

n)Peroxidase

Electro

chem

ical

Glucose

biosensor

[49]

MNPs

(with

oxidaseinmesop

orou

ssilica)

Peroxidase

Colorim

etric

Glucose

andcholesterolbiosensor

[50]

MNPs

(with

oxidaseinmesop

orou

ssilica)

Peroxidase

Colorim

etric

Galactose

biosensor

[51]

MNPs

(with

oxidaseinmesop

orou

ssilica)

Peroxidase

Colorim

etric

Alcoh

olbiosensor

[52]

MNPs

Peroxidase

Colorim

etric

Nucleicacid

detection(Chlam

ydiatra

chom

atis)

[53]

CeO2NPs

Oxidase

Colorim

etric

Nucleicacid

detection(Chlam

ydiatra

chom

atis)

[56]

Chito

san-mod

ified

MNPs

with

thrombinaptamers

Peroxidase

Colorim

etric

Thrombindetection

[57]

Immun

oassay

MNPs

Peroxidase

Colorim

etric

Cardiactropo

ninI(Tn

I)detection

[9]

MNPs-PtN

Psin

mesop

orou

scarbo

nPeroxidase

Colorim

etric

Rotavirusa

ndHER

2detection

[33]

Graph

eneo

xide

Peroxidase

Colorim

etric

Prostatespecifica

ntigen

(PSA

)detectio

n[41]

Chito

san-mod

ified

MNPs

Peroxidase

Colorim

etric

Mou

seIgGandcarcinoembryonica

ntigen

detection

[63]

Prussia

nblue

mod

ified120574-Fe 2O3NPs

Peroxidase

Colorim

etric

IgGdetection

[64]

Ferritins

Peroxidase

Fluo

rometric

Avidin

andhu

man

ceruloplasmin

detection

[65]

MNPs

Peroxidase

Colorim

etric

Rotavirusa

ndHER

2detection

[66]

MNPs-PtN

Pson

graphene

oxide

Peroxidase

Colorim

etric

fluo

rometric

HER

2detectionandim

aging

[35]

Cancer

diagno

stics

(with

outimmun

ereactio

n)andtherapy

Poly(acrylicacid)-coated

CeO2NPs

Oxidase

Colorim

etric

Lung

cancer

celldetection

[13]

Poly(acrylicacid)-coated

CeO2NPs

Oxidase

Colorim

etric

Lung

andbreastcancer

celldetection

[69]

MagnetoferritinNPs

Peroxidase

Colorim

etric

fluo

rometric

Cancer

cellim

aging

[70]

CeO2NPs

Superoxide

dism

utase

Preventio

nof

retin

aldegeneratio

n[74]

CeO2NPs

Superoxide

dism

utase

Anti-infl

ammation

[75]

Superparam

agnetic

ironoxideN

PsPeroxidase

Prom

otionof

stem

cellgrow

th[76]

Environm

ental

engineering

MNPs

(with

oxidaseinmesop

orou

scarbo

n)Peroxidase

Electro

chem

ical

Phenolcresolandcathecho

ldetectio

n[49]

MNPs

Peroxidase

Colorim

etric

Mela

mined

etectio

n[77]

MNPs

Peroxidase

Removalof

phenol

[78]

MNPs

Peroxidase

Removalof

methylene

blue

[79]

MNPs

Peroxidase

Biofi

lmdegradation

[80]

8 Journal of Nanomaterials

proteins and polysaccharides) as well as killing residentbacteria

4 Conclusions and Future Research Aspects

Nanozymes have recently emerged as a potent alternativeto natural enzymes As discussed above although they arestill in the initial stages of research their use has developedsubstantially inmanydifferent detection and treatmentmeth-ods for biomolecules (Table 1) Despite the advantages ofnanozymes such as their low cost high stability robustnessease of mass production and long-term storability thereare several challenges to be tackled for practical use Firstlymost nanozymes have low activity compared to naturalenzymes Even if the nanomaterial itself is highly activeadditional coating and surface modification can decrease itsperformance Therefore development of novel nanozymesexhibiting high activity and appropriate surface-modificationtechniques are the emerging issues in the field of nanozymesNanozymes also have low selectivity to targets owing to theabsence of active sites where a substrate molecule binds andundergoes a chemical reaction in a natural enzyme Althoughresearchers have designed various types of surface-modifiednanozymes with polymers nucleic acids and antibodiesto provide selectivity mimicking natural enzymes this isstill insufficient for use in practical applications Toxicity ofnanozymes to humans and the ecosystem is also an essentialissue to be solved in regard to environmental and therapeuticapplications

In order for nanozymes to be positioned as a novelsource technology by efficiently overcoming the limitationsof natural enzymes we offer the following suggestions Thedevelopment of new nanozymes with higher activity andother positive properties than existing nanozymes is requiredWhile traditional research on developing nanozymes hasbeen performed by random screening of the enzyme-like activities of existing unspecified nanomaterials futureresearch will follow a strategy of rational screening ofenzyme-like activity based on those atomic compositionswhich are envisaged to catalyze enzymatic reactions Fur-thermore a strategy to prepare composites can be expectedto resolve the current major limitations of nanozymes oflow catalytic activity by exploiting their synergistic effectto facilitate electron transfer between composite materialsduring redox reaction Bioinspired synthesis of nanozymesalso provides an option to prepare nontoxic nanozymesby effectively circumventing the use of toxic chemicals inconventional chemical synthesis thereby accelerating theiruse in therapeutic applications Finally the developmentof novel surface engineering technology that can makenanozymes selective to target substrates will be importantin this field With the abovementioned research projects weexpect nanozymes to be widely employed in a wide range ofapplications in the near future

Conflict of Interests

The authors declare no financial or commercial conflict ofinterests

Acknowledgments

This work was supported by the Basic Science ResearchProgram through theNational Research Foundation of Korea(NRF) funded by the Ministry of Science ICT amp FuturePlanning (NRF-2014R1A1A1006016) and by the Gachon Uni-versity research fund of 2014 (GCU-2014-0110)

References

[1] D L Nelson and M M Cox Lehninger Principles of Biochem-istry vol 6 chapter 6 W H Freeman New York NY USA2005

[2] Z Liu R Cai L Mao H Huang and W Ma ldquoHighly sensitivespectrofluorimetric determination of hydrogen peroxide with120573-cyclodextrin-hemin as catalystrdquo Analyst vol 124 no 2 pp173ndash176 1999

[3] R P Bonar-Law and J K M Sanders ldquoPolyol recognition bya steroid-capped porphyrin Enhancement and modulation ofmisfit guest binding by added water or methanolrdquo Journal of theAmerican Chemical Society vol 117 no 1 pp 259ndash271 1995

[4] X-M Huang M Zhu L-Y Mao and H-X Shen ldquoCat-alytic determination of hydrogen peroxide by using themolybdenum-porphyrin complex as a mimetic enzyme ofperoxidaserdquo Analytical Sciences vol 13 no 1 pp 145ndash147 1997

[5] L Fruk andCMNiemeyer ldquoCovalent hemin-DNAadducts forgenerating a novel class of artificial heme enzymesrdquoAngewandteChemiemdashInternational Edition vol 44 no 17 pp 2603ndash26062005

[6] Q Wang Z Yang X Zhang X Xiao C K Chang and B XuldquoA supramolecular-hydrogel-encapsulated hemin as an artifi-cial enzyme to mimic peroxidaserdquo Angewandte Chemie Inter-national Edition vol 46 no 23 pp 4285ndash4289 2007

[7] Z Genfa and P K Dasgupta ldquoHematin as a peroxidase sub-stitute in hydrogen peroxide determinationsrdquo Analytical Chem-istry vol 64 no 5 pp 517ndash522 1992

[8] H Wei and E Wang ldquoNanomaterials with enzyme-like char-acteristics (nanozymes) next-generation artificial enzymesrdquoChemical Society Reviews vol 42 no 14 pp 6060ndash6093 2013

[9] L Gao J Zhuang LNie et al ldquoIntrinsic peroxidase-like activityof ferromagnetic nanoparticlesrdquo Nature Nanotechnology vol 2no 9 pp 577ndash583 2007

[10] R Polsky R Gill L Kaganovsky and I Willner ldquoNucleic acid-functionalized Pt nanoparticles catalytic labels for the ampli-fied electrochemical detection of biomoleculesrdquo AnalyticalChemistry vol 78 no 7 pp 2268ndash2271 2006

[11] T Li Y Du and E Wang ldquoPolyethyleneimine-functionalizedplatinum nanoparticles with high electrochemiluminescenceactivity and their applications to amplified analysis of bio-moleculesrdquo ChemistrymdashAn Asian Journal vol 3 no 11 pp1942ndash1948 2008

[12] W W He Y Liu J S Yuan et al ldquoAuPt nanostructures asoxidase and peroxidase mimetics for use in immunoassaysrdquoBiomaterials vol 32 no 4 pp 1139ndash1147 2011

[13] A Asati S Santra C Kaittanis S Nath and J M PerezldquoOxidase-like activity of polymer-coated cerium oxide nano-partielesrdquo Angewandte ChemiemdashInternational Edition vol 48no 13 pp 2308ndash2312 2009

[14] W J Luo C F Zhu S Su et al ldquoSelf-catalyzed self-limitinggrowth of glucose oxidase-mimicking gold nanoparticlesrdquo ACSNano vol 4 no 12 pp 7451ndash7458 2010

Journal of Nanomaterials 9

[15] X Zheng Q Liu C Jing et al ldquoCatalytic gold nanoparticles fornanoplasmonic detection of DNA hybridizationrdquo AngewandteChemie International Edition vol 50 no 50 pp 11994ndash119982011

[16] Y J Long Y F Li Y Liu J J Zheng J Tang and C JHuang ldquoVisual observation of the mercury-stimulated peroxi-dase mimetic activity of gold nanoparticlesrdquo Chemical Commu-nications vol 47 no 43 pp 11939ndash11941 2011

[17] W Chen J Chen Y-B Feng et al ldquoPeroxidase-like activityof water-soluble cupric oxide nanoparticles and its analyticalapplication for detection of hydrogen peroxide and glucoserdquoAnalyst vol 137 no 7 pp 1706ndash1712 2012

[18] W Luo Y-S Li J Yuan et al ldquoUltrasensitive fluorometricdetermination of hydrogen peroxide and glucose by usingmultiferroic BiFeO

3nanoparticles as a catalystrdquo Talanta vol 81

no 3 pp 901ndash907 2010[19] S H He W B Shi X D Zhang J A Li and Y M Huang ldquo120573-

Cyclodextrins-based inclusion complexes of CoFe2O4magnetic

nanoparticles as catalyst for the luminol chemiluminescencesystem and their applications in hydrogen peroxide detectionrdquoTalanta vol 82 no 1 pp 377ndash383 2010

[20] W B Shi X D Zhang S H He and Y M Huang ldquoCoFe2O4

magnetic nanoparticles as a peroxidasemimicmediated chemi-luminescence for hydrogen peroxide and glucoserdquo ChemicalCommunications vol 47 no 38 pp 10785ndash10787 2011

[21] Y W Fan and Y M Huang ldquoThe effective peroxidase-likeactivity of chitosan-functionalized CoFe

2O4nanoparticles for

chemiluminescence sensing of hydrogen peroxide and glucoserdquoAnalyst vol 137 no 5 pp 1225ndash1231 2012

[22] A K Dutta S K Maji D N Srivastava et al ldquoSynthesis ofFeS and FeSe nanoparticles from a single source precursor astudy of their photocatalytic activity peroxidase-like behaviorand electrochemical sensing of H

2O2rdquo ACS Applied Materials

and Interfaces vol 4 no 4 pp 1919ndash1927 2012[23] Y Song K Qu C Zhao J Ren and X Qu ldquoGraphene oxide

intrinsic peroxidase catalytic activity and its application toglucose detectionrdquoAdvancedMaterials vol 22 no 19 pp 2206ndash2210 2010

[24] Y Song X Wang C Zhao K Qu J Ren and X Qu ldquoLabel-free colorimetric detection of single nucleotide polymorphismby using single-walled carbon nanotube intrinsic peroxidase-like activityrdquo ChemistrymdashA European Journal vol 16 no 12 pp3617ndash3621 2010

[25] Y Guo J Li and S Dong ldquoHemin functionalized graphenenanosheets-based dual biosensor platforms for hydrogen per-oxide and glucoserdquo Sensors and Actuators B Chemical vol 160no 1 pp 295ndash300 2011

[26] J Xie X Zhang H Wang H Zheng Y Huang and J XieldquoAnalytical and environmental applications of nanoparticles asenzyme mimeticsrdquo TrACmdashTrends in Analytical Chemistry vol39 pp 114ndash129 2012

[27] A K Gupta and M Gupta ldquoSynthesis and surface engineeringof iron oxide nanoparticles for biomedical applicationsrdquoBioma-terials vol 26 no 18 pp 3995ndash4021 2005

[28] J Mu Y Wang M Zhao and L Zhang ldquoIntrinsic peroxidase-like activity and catalase-like activity of Co

3O4nanoparticlesrdquo

Chemical Communications vol 48 no 19 pp 2540ndash2542 2012[29] Y Wan P Qi D Zhang J Wu and Y Wang ldquoMan-

ganese oxide nanowire-mediated enzyme-linked immunosor-bent assayrdquo Biosensors and Bioelectronics vol 33 no 1 pp 69ndash74 2012

[30] R Andre F Natalio M Humanes et al ldquoV2O5nanowires

with an intrinsic peroxidase-like activityrdquo Advanced FunctionalMaterials vol 21 no 3 pp 501ndash509 2011

[31] W Chen J Chen A-L Liu L-M Wang G-W Li and X-H Lin ldquoPeroxidase-like activity of cupric oxide nanoparticlerdquoChemCatChem vol 3 no 7 pp 1151ndash1154 2011

[32] Y-L DongH-G Zhang Z U Rahman et al ldquoGraphene oxide-Fe3O4magnetic nanocomposites with peroxidase-like activity

for colorimetric detection of glucoserdquo Nanoscale vol 4 no 13pp 3969ndash3976 2012

[33] M I Kim Y Ye M-A Woo J Lee and H G Park ldquoA highlyefficient colorimetric immunoassay using a nanocompositeentrapping magnetic and platinum nanoparticles in orderedmesoporous carbonrdquo Advanced Healthcare Materials vol 3 no1 pp 36ndash41 2014

[34] J Liu X Hu S Hou et al ldquoAuPt coreshell nanorods withperoxidase- and ascorbate oxidase-like activities for improveddetection of glucoserdquo Sensors and Actuators B Chemical vol166-167 pp 708ndash714 2012

[35] M I Kim M S Kim M-AWoo et al ldquoHighly efficient colori-metric detection of target cancer cells utilizing superior catalyticactivity of graphene oxide-magnetic-platinum nanohybridsrdquoNanoscale vol 6 no 3 pp 1529ndash1536 2014

[36] M Liu H Zhao S Chen H Yu and X Quan ldquoInterface engi-neering catalytic graphene for smart colorimetric biosensingrdquoACS Nano vol 6 no 4 pp 3142ndash3151 2012

[37] Y Ye T Kong X Yu YWu K Zhang and XWang ldquoEnhancednonenzymatic hydrogen peroxide sensing with reducedgraphene oxideferroferric oxide nanocompositesrdquo Talantavol 89 pp 417ndash421 2012

[38] R Cui Z Han and J-J Zhu ldquoHelical carbon nanotubesintrinsic peroxidase catalytic activity and its application forbiocatalysis and biosensingrdquo ChemistrymdashA European Journalvol 17 no 34 pp 9377ndash9384 2011

[39] M Liu H Zhao S Chen H Yu and X Quan ldquoStimuli-responsive peroxidase mimicking at a smart graphene inter-facerdquo Chemical Communications vol 48 no 56 pp 7055ndash70572012

[40] S Liu J Tian L Wang Y Luo and X Sun ldquoA general strategyfor the production of photoluminescent carbon nitride dotsfrom organic amines and their application as novel peroxidase-like catalysts for colorimetric detection of H

2O2and glucoserdquo

RSC Advances vol 2 no 2 pp 411ndash413 2012[41] F Qu T Li and M Yang ldquoColorimetric platform for visual

detection of cancer biomarker based on intrinsic peroxidaseactivity of graphene oxiderdquo Biosensors and Bioelectronics vol26 no 9 pp 3927ndash3931 2011

[42] W Shi QWang Y Long et al ldquoCarbon nanodots as peroxidasemimetics and their applications to glucose detectionrdquo ChemicalCommunications vol 47 no 23 pp 6695ndash6697 2011

[43] X Wang K Qu B Xu J Ren and X Qu ldquoMulticolorluminescent carbon nanoparticles synthesis supramolecularassembly with porphyrin intrinsic peroxidase-like catalyticactivity and applicationsrdquo Nano Research vol 4 no 9 pp 908ndash920 2011

[44] H Wei and E Wang ldquoFe3O4magnetic nanoparticles as per-

oxidase mimetics and their applications in H2O2and glucose

detectionrdquo Analytical Chemistry vol 80 no 6 pp 2250ndash22542008

[45] Q Chang KDeng L ZhuG Jiang C Yu andH Tang ldquoDeter-mination of hydrogen peroxide with the aid of peroxidase-like

10 Journal of Nanomaterials

Fe3O4magnetic nanoparticles as the catalystrdquo Microchimica

Acta vol 165 no 3-4 pp 299ndash305 2009[46] Z Jiang L Kun H Ouyang A Liang and H Jiang ldquoA simple

and sensitive fluorescence quenching method for the determi-nation of H

2O2using rhodamine B and Fe

3O4nanocatalystrdquo

Journal of Fluorescence vol 21 no 5 pp 2015ndash2020 2011[47] Y Jv B Li andR Cao ldquoPositively-charged gold nanoparticles as

peroxidiase mimic and their application in hydrogen peroxideand glucose detectionrdquo Chemical Communications vol 46 no42 pp 8017ndash8019 2010

[48] K Wang J-J Xu D-C Sun H Wei and X-H Xia ldquoSelectiveglucose detection based on the concept of electrochemicaldepletion of electroactive species in diffusion layerrdquo Biosensorsand Bioelectronics vol 20 no 7 pp 1366ndash1372 2005

[49] M I Kim Y Ye B Y Won S Shin J Lee and H G Park ldquoAhighly efficient electrochemical biosensing platform by employ-ing conductive nanocomposite entrapping magnetic nano-particles and oxidase in mesoporous carbon foamrdquo AdvancedFunctional Materials vol 21 no 15 pp 2868ndash2875 2011

[50] M I Kim J Shim T Li J Lee and H G Park ldquoFabrica-tion of nanoporous nanocomposites entrapping Fe

3O4mag-

netic nanoparticles and oxidases for colorimetric biosensingrdquoChemistrymdashAEuropean Journal vol 17 no 38 pp 10700ndash107072011

[51] M I Kim J Shim T Li et al ldquoColorimetric quantificationof galactose using a nanostructured multi-catalyst systementrapping galactose oxidase and magnetic nanoparticles asperoxidasemimeticsrdquoAnalyst vol 137 no 5 pp 1137ndash1143 2012

[52] M I Kim J Shim H J Parab S C Shin J Lee and H G ParkldquoA convenient alcohol sensor using one-pot nanocompositeentrapping alcohol oxidase and magnetic nanoparticles as per-oxidase mimeticsrdquo Journal of Nanoscience and Nanotechnologyvol 12 no 7 pp 5914ndash5919 2012

[53] K S Park M I Kim D-Y Cho and H G Park ldquoLabel-free colorimetric detection of nucleic acids based on target-induced shielding against the peroxidase-mimicking activity ofmagnetic nanoparticlesrdquo Small vol 7 no 11 pp 1521ndash1525 2011

[54] J A Brinkman M Z Rahmani W E Jones A K Chaturvediand M E Hagensee ldquoOptimization of PCR based detection ofhuman papillomavirus DNA from urine specimensrdquo Journal ofClinical Virology vol 29 no 4 pp 230ndash240 2004

[55] L Hafner K Beagley and P Timms ldquoChlamydia trachomatisinfection host immune responses and potential vaccinesrdquoMucosal Immunology vol 1 no 2 pp 116ndash130 2008

[56] M I Kim K S Park and H G Park ldquoUltrafast colorimetricdetection of nucleic acids based on the inhibition of the oxidaseactivity of cerium oxide nanoparticlesrdquo Chemical Communica-tions vol 50 no 67 pp 9577ndash9580 2014

[57] Z Zhang Z Wang X Wang and X Yang ldquoMagneticnanoparticle-linked colorimetric aptasensor for the detection ofthrombinrdquo Sensors and Actuators B Chemical vol 147 no 2 pp428ndash433 2010

[58] B W Blais and A Martinez-Perez ldquoDetection of groupD salmonellae including Salmonella enteritidis in eggs bypolymyxin-based enzyme-linked immunosorbent assayrdquo Jour-nal of Food Protection vol 71 no 2 pp 392ndash396 2008

[59] V Tripathi S Nara S K Chaube et al ldquoDevelopment ofrapid and sensitive one-step direct enzyme linked immunosor-bent assay for 17-120572-OH-progesterone in serumrdquo Journal ofImmunoassay and Immunochemistry vol 29 no 2 pp 117ndash1272008

[60] K DMcReynolds M J Hadd and J Gervay-Hague ldquoSynthesisof biotinylated glycoconjugates and their use in a novel ELISAfor direct comparison ofHIV-1 gp120 recognition ofGalCer andrelated carbohydrate analoguesrdquo Bioconjugate Chemistry vol10 no 6 pp 1021ndash1031 1999

[61] H Hocini S Iscaki J-P Bouvet M D Kazatchkine and LBelec ldquoAn ELISA method to measure total and specific humansecretory IgA subclasses based on selective degradation by IgA1-proteaserdquo Journal of Immunological Methods vol 235 no 1-2pp 53ndash60 2000

[62] L Micheli S Di Stefano D Moscone et al ldquoProduction ofantibodies and development of highly sensitive formats ofenzyme immunoassay for saxitoxin analysisrdquo Analytical andBioanalytical Chemistry vol 373 no 8 pp 678ndash684 2002

[63] L Gao J Wu S Lyle K Zehr L Cao and D Gao ldquoMagnetitenanoparticle-linked immunosorbent assayrdquo Journal of PhysicalChemistry C vol 112 no 44 pp 17357ndash17361 2008

[64] X-Q Zhang S-W Gong Y Zhang T Yang C-YWang andNGu ldquoPrussian blue modified iron oxide magnetic nanoparticlesand their high peroxidase-like activityrdquo Journal of MaterialsChemistry vol 20 no 24 pp 5110ndash5116 2010

[65] Z Tang H Wu Y Zhang Z Li and Y Lin ldquoEnzyme-mimicactivity of ferric nano-core residing in ferritin and its biosensingapplicationsrdquo Analytical Chemistry vol 83 no 22 pp 8611ndash8616 2011

[66] M-A Woo M I Kim J H Jung K S Park T S Seoand H G Park ldquoA novel colorimetric immunoassay utilizingthe peroxidase mimicking activity of magnetic nanoparticlesrdquoInternational Journal of Molecular Sciences vol 14 no 5 pp9999ndash10014 2013

[67] V H C Bramwell G S Doig A B Tuck et al ldquoChangesover time of extracellular domain of HER2 (ECDHER2) serumlevels have prognostic value in metastatic breast cancerrdquo BreastCancer Research andTreatment vol 114 no 3 pp 503ndash511 2009

[68] K S Asgeirsson A Agrawal C Allen et al ldquoSerum epidermalgrowth factor receptor and HER2 expression in primary andmetastatic breast cancer patientsrdquo Breast Cancer Research vol9 no 6 article R75 2007

[69] A Asati C Kaittanis S Santra and J M Perez ldquoPH-tunableoxidase-like activity of cerium oxide nanoparticles achievingsensitive fluorigenic detection of cancer biomarkers at neutralpHrdquo Analytical Chemistry vol 83 no 7 pp 2547ndash2553 2011

[70] K L Fan C Q Cao Y X Pan et al ldquoMagnetoferritinnanoparticles for targeting and visualizing tumour tissuesrdquoNature Nanotechnology vol 7 no 7 pp 459ndash464 2012

[71] S Beatty H-H Koh M Phil D Henson and M BoultonldquoThe role of oxidative stress in the pathogenesis of age-relatedmacular degenerationrdquo Survey of Ophthalmology vol 45 no 2pp 115ndash134 2000

[72] C Korsvik S Patil S Seal and W T Self ldquoSuperoxidedismutase mimetic properties exhibited by vacancy engineeredceria nanoparticlesrdquo Chemical Communications no 10 pp1056ndash1058 2007

[73] E G Heckert A S Karakoti S Seal andW T Self ldquoThe role ofcerium redox state in the SOD mimetic activity of nanoceriardquoBiomaterials vol 29 no 18 pp 2705ndash2709 2008

[74] J Chen S Patil S Seal and J F McGinnis ldquoRare earthnanoparticles prevent retinal degeneration induced by intracel-lular peroxidesrdquo Nature Nanotechnology vol 1 no 2 pp 142ndash150 2006

Journal of Nanomaterials 11

[75] S M Hirst A S Karakoti R D Tyler N Sriranganathan SSeal and C M Reilly ldquoAnti-inflammatory properties of ceriumoxide nanoparticlesrdquo Small vol 5 no 24 pp 2848ndash2856 2009

[76] D-M Huang J-K Hsiao Y-C Chen et al ldquoThe promotion ofhuman mesenchymal stem cell proliferation by superparamag-netic iron oxide nanoparticlesrdquo Biomaterials vol 30 no 22 pp3645ndash3651 2009

[77] N Ding N Yan C Ren and X Chen ldquoColorimetric determi-nation of melamine in dairy products by Fe

3O4Magnetic nano-

particles-H2O2-ABTS detection systemrdquo Analytical Chemistry

vol 82 no 13 pp 5897ndash5899 2010[78] J Zhang J Zhuang L Gao et al ldquoDecomposing phenol by the

hidden talent of ferromagnetic nanoparticlesrdquo Chemospherevol 73 no 9 pp 1524ndash1528 2008

[79] J Z Jiang J Zou L H Zhu L Huang H Jiang and YZhang ldquoDegradation of methylene blue with H

2O2activated

by peroxidase-like Fe3O4magnetic nanoparticlesrdquo Journal of

Nanoscience and Nanotechnology vol 11 no 6 pp 4793ndash47992011

[80] L Gao K M Giglio J L Nelson H Sondermann and AJ Travis ldquoFerromagnetic nanoparticles with peroxidase-likeactivity enhance the cleavage of biological macromolecules forbiofilm eliminationrdquo Nanoscale vol 6 no 5 pp 2588ndash25932014

[81] K Vickery A Pajkos and Y Cossart ldquoRemoval of biofilmfrom endoscopes evaluation of detergent efficiencyrdquo AmericanJournal of Infection Control vol 32 no 3 pp 170ndash176 2004

Submit your manuscripts athttpwwwhindawicom

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CorrosionInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Polymer ScienceInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CeramicsJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CompositesJournal of

NanoparticlesJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

Biomaterials

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

NanoscienceJournal of

TextilesHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Journal of

NanotechnologyHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

CrystallographyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CoatingsJournal of

Advances in

Materials Science and EngineeringHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Smart Materials Research

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MetallurgyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

MaterialsJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Nano

materials

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal ofNanomaterials

Page 5: Review Article Recent Research Trends and Future …downloads.hindawi.com/journals/jnm/2015/756278.pdfnovel biosensor, immunoassay, cancer diagnostics, therapeutics, and environmental

Journal of Nanomaterials 5

was also developed to detect CEA by employing themagneticproperties of CS-MNPs which facilitate capturing separat-ing and enriching antigens as well as redispersing the MNPaggregation in solution

Zhang and coworkers reported a novel immunoassayutilizing Prussian blue modified 120574-Fe

2O3NPs [64] Prus-

sian blue a dark blue pigment with the idealized formulaFe7(CN)18 was modified on the surface of 120574-Fe

2O3NPs due

to its excellent electrochemical behavior that accelerated elec-tron transfer and its catalytic properties that could catalyzethe reduction of H

2O2 Prussian blue modified 120574-Fe

2O3NPs

(PBMNPs) were next conjugated with staphylococcal proteinA (SPA) to bind to IgG immobilized in the well so thatPBMNPs could derive a colorimetric reaction in the presenceof TMB and H

2O2

Ferritins nanoscale globular protein cages encapsulatinga ferric core were used in immunoassay in Tang et alrsquos study[65] In this study ferritin showed a thermally stable and pH-tolerable enzyme-mimetic activity derived from the ferricnanocore of ferritin Two forms of immunoassay systemswere constructed antigen-down type and sandwich typeAvidin was selected as the target molecule of the antigen-down immunoassay and nitrated human ceruloplasmin asthe target molecule of the sandwich-type immunoassayTheyalso reported that the ferritins could be utilized in analyticalapplications such as H

2O2assay In their assay ferritin

oxidizes the p-HPPA in the presence of H2O2to generate

a fluorescent product This ferritin-based H2O2assay shows

a detection limit of 016 120583M and a linear detection range of40 120583M which is one-order higher sensitivity with a broaderlinear response range

Immunoassay systems for detection of rotavirus andbreast cancer have been developed [66] in which MNPsare conjugated to antibodies against rotaviruses and humanepidermal growth factor receptor 2 (HER2) In this sys-tem sandwich-type and antigen-down type immunoassaywere used to detect rotavirus and HER2 respectively Forthe detection of rotavirus rotavirus antibodies were firstimmobilized in a well and rotavirus bound to the immo-bilized antibody Subsequently MNP-conjugated antibodies(MNP-Abs) were added to the well in order to bind tocaptured rotaviruses Finally the peroxidase substrate TMBwas changed into blue-colored products in the presence ofH2O2 An antigen-down immunoassay system was used in

the case of breast cell detection which did not require priorimmobilization of antibodies in the bare well surface Breastcells were cultured in a well so that they adsorbed to thesurface of the well MNPs-Abs were then applied to the cell-cultured well followed by adding TMB and H

2O2to induce

a colorimetric reactionThis assay system displayed excellentspecificity sensitivity and linearity for quantitative detectionof the target molecules as well as the production of a colorsignal that could be detected by the naked eye

Based on the above system a nanocomposite-basedimmunoassay was also performed in which nanocompositeentrappingMNPs and Pt NPs in ordered mesoporous carbon(OMC) were utilized instead of HRP [33]This immunoassaygenerated significantly higher absorption intensity of colorsignal than the current ELISA and was able to quantify the

target antigen very rapidly within three minutes while theconventional ELISA requires several tens of minutes for colorsignal development [67 68] It showed a limit of detection(LOD) for HER2 of 15 ngmLminus1 in the linear range from 25 to100 ngmLminus1 The nanocomposite was found to have 50 timeshigher catalytic efficiency than that of free MNPs owing tothe high catalytic action of Pt NPs

Graphene oxide (GO) has been used in immunoassay as aperoxidase-mimicking nanozyme [41] Yanrsquos group developeda sandwich-type immunoassay for the detection of cancerbiomarker prostate specific antigen (PSA) In this work amagnetic bead (MB) was used to immobilize the primaryPSA antibody (Ab

1) and then a GO-conjugated secondary

antibody (Ab2) was applied in the presence of PSA Subse-

quentlyMB-Ab1was separated from the immunocomplex by

an external magnetic field and GO catalyzed the oxidation ofhydroquinone in the presence of H

2O2to generate a brown-

colored productConjugating both MNPs and Pt NPs on the surface of

GO enabled highly sensitive and rapid colorimetric detectionof the target cancer cell [35] In this work it was notablethat the electron transfer between MNPs and Pt NPs createsa synergistic effect significantly enhancing the catalyticperformance of MNPs-Pt NPs-GO nanohybrids Using thisimmunoassay system human breast adenocarcinoma cells(SKBR-3) which overexpressed HER2 were detected in fiveminutes with high specificity and sensitivity The LOD fortarget SKBR-3 cells was found to be about 100 cells in thelinear range from 100 to 1000 cells Moreover fluorescenceimaging of SKBR-3 was successfully performed with MNPs-Pt NPs-GO nanohybrids

322 Other Immunoassays By employing the superparam-agnetic property of MNPs a capture-detection immunoassaysystem has been developed by Gaorsquos group [63] In the proce-dure the CS-MNPs were conjugated with carcinoembryonicantibodies (anti-CEA M111147) and then mixed with thesample containing CEA After the CEA was captured byMNPs a magnetic field was applied to separate the MNPswhich had captured CEA Finally the MNPs capturing CEAwere injected into microplate wells coated with anothermonoclonal CEA antibody creating the sandwich formatThereby the MNPs prompted the generation of a color signalupon addition of colorimetric substrate and H

2O2to the

wells Cardiac troponin I (TnI) in serum a well-knownbiomarker for myocardial infarction was also detected by acapture-detection immunoassay utilizing the magnetism andperoxidase ability of MNPs [9]

33 Cancer Diagnostics without Immune Reaction Asidefrom immunoassay using antigen-antibody interaction othernovel assays using nanozymes have been developed partic-ularly for the diagnosis of tumor cells Asati and coworkersreported an assay for the determination of tumor cellswith poly(acrylic acid)-coated CeO

2NPs (nanoceria) as an

oxidase mimic [13] When the nanoparticles were conjugatedwith folic acid they bound to folate receptors on the tumorcell (A-549 lung cancer cells) due to high expression offolate receptors on the tumor cell surface Polymer-coated

6 Journal of Nanomaterials

nanoceria as an oxidase mimic made detection of tumorcells easier than with traditional immunoassay because itdirectly oxidized a colorimetric substrate to a colored productwithout H

2O2and additional steps to introduce an enzyme-

conjugated secondary antibody Further advances in thistechnology were also reported by employing a fluorescence-generating substrate ampliflu to detect target cancer cells ataround neutral pH [69]

Another interesting study to visualize target tumor tissueswithout the use of any additional targeting ligands hasalso been described [70] In this study peroxidase-like ironoxide nanoparticles were encapsulated inside a recombinanthuman heavy-chain ferritin (Hfn) protein shell which bindsto tumor cells that overexpress transferrin receptor 1The ironoxide cores catalyzed the oxidation of peroxidase substratesin the presence of H

2O2to produce the colorimetric signal

that was used to visualize tumor tissues Through thisstrategy nine types of cancer were successfully verified withenough specificity and sensitivity

34 Therapeutic Applications As described above nano-zymes have been widely used for detection and diagnos-tic methods Besides these applications many researchershave also studied therapeutic applications including anti-inflammatory effects neuroprotection stem cell growth andantiaging In general SOD was often utilized for therapeuticapplications owing to its protective role as a scavenger of reac-tive oxygen intermediates (ROIs) Intracellular concentrationof ROI including hydrogen peroxidase hypochlorite ionshydroxyl radicals hydroxyl ions and superoxide anions hasbeen known to be a cause of cell degeneration and associateddiseases [71] Inspired by earlier studies by Seal et al whichrevealed the activity of CeO

2NPs as a SOD-mimic [72 73]

various studies have been attempted to develop SOD-mimicking nanozymes

Chen at al reported that nanoceria as a SOD-mimicprevented retinal degeneration by inhibiting the productionof ROIs [74] In their work nanoceria prevented ROI-induced apoptosis and intracellular accumulation of ROIin cultured retinal neurons in the presence of H

2O2 They

further demonstrated that nanoceria injected into the eyes ofrats protected retina photoreceptor cells from light-induceddegeneration The study by Hirst et al also demonstratedthat nanoceria could be used for anti-inflammation byelimination of the radical oxygen species in J774A1 murinemacrophage cells [75]

Superparamagnetic iron oxide (SPIO) nanoparticles havebeen employed to promote growth of stem cells Huanget al reported that Ferucarbotran a commercialized SPIOcould promote cell growth in humanmesenchymal stem cells(hMSCs) by diminishing intracellular H

2O2and also accel-

erate cell cycle progression [76] In this report the intrinsicperoxidase-like activity of SPIO dramatically reduced intra-cellular H

2O2after internalization into hMSCs as well as

free iron ions released from lysosomal degradation of SPIO-affected cell cycle control molecules

35 Environmental Engineering Recently environmentalproblems such as water and air pollution food safety and

public health have become growing concerns in societyIn addition to the aforementioned applications nanozyme-based techniques have been explored for use in the field ofenvironmental technology

351 Pollutant Detection Ding et al developed a simpleand rapid colorimetric method for detecting melamine anorganic nitrogenous compound which is toxic when swal-lowed and has been illegally added to dairy products [77]The principle of this method is as follows Melamine inhibitsthe catalytic oxidation of colorimetric substrates (ABTS) byMNPs in the presence of H

2O2 because it competitively

reacts with H2O2 forming an additional compound Conse-

quently the intensity of the ABTS color signal was dependenton the concentration of melamine On the basis of thisreaction a colorimetric systemusingMNPs could enable easydetection by the naked eye of concentrations of melamineabove safety limits in dairy products

Nanocomposite-entrapping MNPs and oxidase in meso-porous carbonwere used to detect several phenol compoundsamperometrically such as phenol cresol and cathechol[49] These phenol compounds produced a concentration-dependent increase of cathodic current in this system whichmay have great potential in the field of environmentalmonitoring

352 Pollutant Removal Although there have been manymethods for removal of industrial dyestuffs such as absorp-tion precipitation and ultrasonic decomposition they couldnot efficiently degrade organic pollutants in wastewaterNanozyme-based methods have been found to be a power-ful cost-effective and simple method for degradation andmineralization of organic dyes from industrial processesMost prominently MNPs such as peroxidase have beeninvestigated for degradation of organic pollutants such asmethylene blue phenol and rhodamine B A MNP-baseddegradation method offers distinct advantages over existingdegradation methods which use HRP such as lower costhigh stability and reusability MNPs-H

2O2could remove

85 of phenol from aqueous solution within three hours[78] The MNPs-based degradation showed higher efficiencycompared to HRP-based degradation and stability in a broadrange of temperatures (5ndash90∘C) leading to ease of storageFurthermore MNPs could be captured by the application ofan external field and recycled for five rounds retaining almost100 of their activity Removal of methylene blue by MNPs-H2O2coupled method has also been successfully performed

by Jiang et al [79] It was observed that 96ofmethylene bluewas degraded in 15 minutes at optimized condition

Gao et al reported that MNPs-H2O2system could

degrade biofilm and kill resident bacteria [80] Biofilm espe-cially formed by Pseudomonas aeruginosa occurs in hospitalwater systems and medical devices with high frequencybecoming a common cause of nosocomial infection [81]In this report MNPs-H

2O2system exhibited significantly

higher efficiency than the use of H2O2in degradation of

biofilm The authors confirmed that additional free hydroxylradicals generated by MNP catalysis of H

2O2facilitated

the oxidative cleavage of biofilm components (nucleic acids

Journal of Nanomaterials 7

Table1Va

rious

applicationstu

dies

basedon

nano

zymes

Applicationfield

Nanozym

esAc

tivity

Detectio

nmetho

dDetails

Ref

Biosensor

MNPs

Peroxidase

Colorim

etric

H2O2biosensor

[9]

AuNPs

Glucose

oxidase

Colorim

etric

Nucleicacid

detection

[15]

Carboxyl-m

odified

graphene

oxide

Peroxidase

Colorim

etric

H2O2andglucoseb

iosensor

[23]

MNPs

Peroxidase

Colorim

etric

H2O2andglucoseb

iosensor

[44]

MNPs

Peroxidase

Colorim

etric

H2O2biosensor

[45]

MNPs

Peroxidase

Colorim

etric

H2O2biosensor

[46]

AuNPs

Peroxidase

Colorim

etric

H2O2andglucoseb

iosensor

[47]

MNPs

Peroxidase

Electro

chem

ical

Glucose

biosensor

[48]

MNPs

(with

oxidaseinmesop

orou

scarbo

n)Peroxidase

Electro

chem

ical

Glucose

biosensor

[49]

MNPs

(with

oxidaseinmesop

orou

ssilica)

Peroxidase

Colorim

etric

Glucose

andcholesterolbiosensor

[50]

MNPs

(with

oxidaseinmesop

orou

ssilica)

Peroxidase

Colorim

etric

Galactose

biosensor

[51]

MNPs

(with

oxidaseinmesop

orou

ssilica)

Peroxidase

Colorim

etric

Alcoh

olbiosensor

[52]

MNPs

Peroxidase

Colorim

etric

Nucleicacid

detection(Chlam

ydiatra

chom

atis)

[53]

CeO2NPs

Oxidase

Colorim

etric

Nucleicacid

detection(Chlam

ydiatra

chom

atis)

[56]

Chito

san-mod

ified

MNPs

with

thrombinaptamers

Peroxidase

Colorim

etric

Thrombindetection

[57]

Immun

oassay

MNPs

Peroxidase

Colorim

etric

Cardiactropo

ninI(Tn

I)detection

[9]

MNPs-PtN

Psin

mesop

orou

scarbo

nPeroxidase

Colorim

etric

Rotavirusa

ndHER

2detection

[33]

Graph

eneo

xide

Peroxidase

Colorim

etric

Prostatespecifica

ntigen

(PSA

)detectio

n[41]

Chito

san-mod

ified

MNPs

Peroxidase

Colorim

etric

Mou

seIgGandcarcinoembryonica

ntigen

detection

[63]

Prussia

nblue

mod

ified120574-Fe 2O3NPs

Peroxidase

Colorim

etric

IgGdetection

[64]

Ferritins

Peroxidase

Fluo

rometric

Avidin

andhu

man

ceruloplasmin

detection

[65]

MNPs

Peroxidase

Colorim

etric

Rotavirusa

ndHER

2detection

[66]

MNPs-PtN

Pson

graphene

oxide

Peroxidase

Colorim

etric

fluo

rometric

HER

2detectionandim

aging

[35]

Cancer

diagno

stics

(with

outimmun

ereactio

n)andtherapy

Poly(acrylicacid)-coated

CeO2NPs

Oxidase

Colorim

etric

Lung

cancer

celldetection

[13]

Poly(acrylicacid)-coated

CeO2NPs

Oxidase

Colorim

etric

Lung

andbreastcancer

celldetection

[69]

MagnetoferritinNPs

Peroxidase

Colorim

etric

fluo

rometric

Cancer

cellim

aging

[70]

CeO2NPs

Superoxide

dism

utase

Preventio

nof

retin

aldegeneratio

n[74]

CeO2NPs

Superoxide

dism

utase

Anti-infl

ammation

[75]

Superparam

agnetic

ironoxideN

PsPeroxidase

Prom

otionof

stem

cellgrow

th[76]

Environm

ental

engineering

MNPs

(with

oxidaseinmesop

orou

scarbo

n)Peroxidase

Electro

chem

ical

Phenolcresolandcathecho

ldetectio

n[49]

MNPs

Peroxidase

Colorim

etric

Mela

mined

etectio

n[77]

MNPs

Peroxidase

Removalof

phenol

[78]

MNPs

Peroxidase

Removalof

methylene

blue

[79]

MNPs

Peroxidase

Biofi

lmdegradation

[80]

8 Journal of Nanomaterials

proteins and polysaccharides) as well as killing residentbacteria

4 Conclusions and Future Research Aspects

Nanozymes have recently emerged as a potent alternativeto natural enzymes As discussed above although they arestill in the initial stages of research their use has developedsubstantially inmanydifferent detection and treatmentmeth-ods for biomolecules (Table 1) Despite the advantages ofnanozymes such as their low cost high stability robustnessease of mass production and long-term storability thereare several challenges to be tackled for practical use Firstlymost nanozymes have low activity compared to naturalenzymes Even if the nanomaterial itself is highly activeadditional coating and surface modification can decrease itsperformance Therefore development of novel nanozymesexhibiting high activity and appropriate surface-modificationtechniques are the emerging issues in the field of nanozymesNanozymes also have low selectivity to targets owing to theabsence of active sites where a substrate molecule binds andundergoes a chemical reaction in a natural enzyme Althoughresearchers have designed various types of surface-modifiednanozymes with polymers nucleic acids and antibodiesto provide selectivity mimicking natural enzymes this isstill insufficient for use in practical applications Toxicity ofnanozymes to humans and the ecosystem is also an essentialissue to be solved in regard to environmental and therapeuticapplications

In order for nanozymes to be positioned as a novelsource technology by efficiently overcoming the limitationsof natural enzymes we offer the following suggestions Thedevelopment of new nanozymes with higher activity andother positive properties than existing nanozymes is requiredWhile traditional research on developing nanozymes hasbeen performed by random screening of the enzyme-like activities of existing unspecified nanomaterials futureresearch will follow a strategy of rational screening ofenzyme-like activity based on those atomic compositionswhich are envisaged to catalyze enzymatic reactions Fur-thermore a strategy to prepare composites can be expectedto resolve the current major limitations of nanozymes oflow catalytic activity by exploiting their synergistic effectto facilitate electron transfer between composite materialsduring redox reaction Bioinspired synthesis of nanozymesalso provides an option to prepare nontoxic nanozymesby effectively circumventing the use of toxic chemicals inconventional chemical synthesis thereby accelerating theiruse in therapeutic applications Finally the developmentof novel surface engineering technology that can makenanozymes selective to target substrates will be importantin this field With the abovementioned research projects weexpect nanozymes to be widely employed in a wide range ofapplications in the near future

Conflict of Interests

The authors declare no financial or commercial conflict ofinterests

Acknowledgments

This work was supported by the Basic Science ResearchProgram through theNational Research Foundation of Korea(NRF) funded by the Ministry of Science ICT amp FuturePlanning (NRF-2014R1A1A1006016) and by the Gachon Uni-versity research fund of 2014 (GCU-2014-0110)

References

[1] D L Nelson and M M Cox Lehninger Principles of Biochem-istry vol 6 chapter 6 W H Freeman New York NY USA2005

[2] Z Liu R Cai L Mao H Huang and W Ma ldquoHighly sensitivespectrofluorimetric determination of hydrogen peroxide with120573-cyclodextrin-hemin as catalystrdquo Analyst vol 124 no 2 pp173ndash176 1999

[3] R P Bonar-Law and J K M Sanders ldquoPolyol recognition bya steroid-capped porphyrin Enhancement and modulation ofmisfit guest binding by added water or methanolrdquo Journal of theAmerican Chemical Society vol 117 no 1 pp 259ndash271 1995

[4] X-M Huang M Zhu L-Y Mao and H-X Shen ldquoCat-alytic determination of hydrogen peroxide by using themolybdenum-porphyrin complex as a mimetic enzyme ofperoxidaserdquo Analytical Sciences vol 13 no 1 pp 145ndash147 1997

[5] L Fruk andCMNiemeyer ldquoCovalent hemin-DNAadducts forgenerating a novel class of artificial heme enzymesrdquoAngewandteChemiemdashInternational Edition vol 44 no 17 pp 2603ndash26062005

[6] Q Wang Z Yang X Zhang X Xiao C K Chang and B XuldquoA supramolecular-hydrogel-encapsulated hemin as an artifi-cial enzyme to mimic peroxidaserdquo Angewandte Chemie Inter-national Edition vol 46 no 23 pp 4285ndash4289 2007

[7] Z Genfa and P K Dasgupta ldquoHematin as a peroxidase sub-stitute in hydrogen peroxide determinationsrdquo Analytical Chem-istry vol 64 no 5 pp 517ndash522 1992

[8] H Wei and E Wang ldquoNanomaterials with enzyme-like char-acteristics (nanozymes) next-generation artificial enzymesrdquoChemical Society Reviews vol 42 no 14 pp 6060ndash6093 2013

[9] L Gao J Zhuang LNie et al ldquoIntrinsic peroxidase-like activityof ferromagnetic nanoparticlesrdquo Nature Nanotechnology vol 2no 9 pp 577ndash583 2007

[10] R Polsky R Gill L Kaganovsky and I Willner ldquoNucleic acid-functionalized Pt nanoparticles catalytic labels for the ampli-fied electrochemical detection of biomoleculesrdquo AnalyticalChemistry vol 78 no 7 pp 2268ndash2271 2006

[11] T Li Y Du and E Wang ldquoPolyethyleneimine-functionalizedplatinum nanoparticles with high electrochemiluminescenceactivity and their applications to amplified analysis of bio-moleculesrdquo ChemistrymdashAn Asian Journal vol 3 no 11 pp1942ndash1948 2008

[12] W W He Y Liu J S Yuan et al ldquoAuPt nanostructures asoxidase and peroxidase mimetics for use in immunoassaysrdquoBiomaterials vol 32 no 4 pp 1139ndash1147 2011

[13] A Asati S Santra C Kaittanis S Nath and J M PerezldquoOxidase-like activity of polymer-coated cerium oxide nano-partielesrdquo Angewandte ChemiemdashInternational Edition vol 48no 13 pp 2308ndash2312 2009

[14] W J Luo C F Zhu S Su et al ldquoSelf-catalyzed self-limitinggrowth of glucose oxidase-mimicking gold nanoparticlesrdquo ACSNano vol 4 no 12 pp 7451ndash7458 2010

Journal of Nanomaterials 9

[15] X Zheng Q Liu C Jing et al ldquoCatalytic gold nanoparticles fornanoplasmonic detection of DNA hybridizationrdquo AngewandteChemie International Edition vol 50 no 50 pp 11994ndash119982011

[16] Y J Long Y F Li Y Liu J J Zheng J Tang and C JHuang ldquoVisual observation of the mercury-stimulated peroxi-dase mimetic activity of gold nanoparticlesrdquo Chemical Commu-nications vol 47 no 43 pp 11939ndash11941 2011

[17] W Chen J Chen Y-B Feng et al ldquoPeroxidase-like activityof water-soluble cupric oxide nanoparticles and its analyticalapplication for detection of hydrogen peroxide and glucoserdquoAnalyst vol 137 no 7 pp 1706ndash1712 2012

[18] W Luo Y-S Li J Yuan et al ldquoUltrasensitive fluorometricdetermination of hydrogen peroxide and glucose by usingmultiferroic BiFeO

3nanoparticles as a catalystrdquo Talanta vol 81

no 3 pp 901ndash907 2010[19] S H He W B Shi X D Zhang J A Li and Y M Huang ldquo120573-

Cyclodextrins-based inclusion complexes of CoFe2O4magnetic

nanoparticles as catalyst for the luminol chemiluminescencesystem and their applications in hydrogen peroxide detectionrdquoTalanta vol 82 no 1 pp 377ndash383 2010

[20] W B Shi X D Zhang S H He and Y M Huang ldquoCoFe2O4

magnetic nanoparticles as a peroxidasemimicmediated chemi-luminescence for hydrogen peroxide and glucoserdquo ChemicalCommunications vol 47 no 38 pp 10785ndash10787 2011

[21] Y W Fan and Y M Huang ldquoThe effective peroxidase-likeactivity of chitosan-functionalized CoFe

2O4nanoparticles for

chemiluminescence sensing of hydrogen peroxide and glucoserdquoAnalyst vol 137 no 5 pp 1225ndash1231 2012

[22] A K Dutta S K Maji D N Srivastava et al ldquoSynthesis ofFeS and FeSe nanoparticles from a single source precursor astudy of their photocatalytic activity peroxidase-like behaviorand electrochemical sensing of H

2O2rdquo ACS Applied Materials

and Interfaces vol 4 no 4 pp 1919ndash1927 2012[23] Y Song K Qu C Zhao J Ren and X Qu ldquoGraphene oxide

intrinsic peroxidase catalytic activity and its application toglucose detectionrdquoAdvancedMaterials vol 22 no 19 pp 2206ndash2210 2010

[24] Y Song X Wang C Zhao K Qu J Ren and X Qu ldquoLabel-free colorimetric detection of single nucleotide polymorphismby using single-walled carbon nanotube intrinsic peroxidase-like activityrdquo ChemistrymdashA European Journal vol 16 no 12 pp3617ndash3621 2010

[25] Y Guo J Li and S Dong ldquoHemin functionalized graphenenanosheets-based dual biosensor platforms for hydrogen per-oxide and glucoserdquo Sensors and Actuators B Chemical vol 160no 1 pp 295ndash300 2011

[26] J Xie X Zhang H Wang H Zheng Y Huang and J XieldquoAnalytical and environmental applications of nanoparticles asenzyme mimeticsrdquo TrACmdashTrends in Analytical Chemistry vol39 pp 114ndash129 2012

[27] A K Gupta and M Gupta ldquoSynthesis and surface engineeringof iron oxide nanoparticles for biomedical applicationsrdquoBioma-terials vol 26 no 18 pp 3995ndash4021 2005

[28] J Mu Y Wang M Zhao and L Zhang ldquoIntrinsic peroxidase-like activity and catalase-like activity of Co

3O4nanoparticlesrdquo

Chemical Communications vol 48 no 19 pp 2540ndash2542 2012[29] Y Wan P Qi D Zhang J Wu and Y Wang ldquoMan-

ganese oxide nanowire-mediated enzyme-linked immunosor-bent assayrdquo Biosensors and Bioelectronics vol 33 no 1 pp 69ndash74 2012

[30] R Andre F Natalio M Humanes et al ldquoV2O5nanowires

with an intrinsic peroxidase-like activityrdquo Advanced FunctionalMaterials vol 21 no 3 pp 501ndash509 2011

[31] W Chen J Chen A-L Liu L-M Wang G-W Li and X-H Lin ldquoPeroxidase-like activity of cupric oxide nanoparticlerdquoChemCatChem vol 3 no 7 pp 1151ndash1154 2011

[32] Y-L DongH-G Zhang Z U Rahman et al ldquoGraphene oxide-Fe3O4magnetic nanocomposites with peroxidase-like activity

for colorimetric detection of glucoserdquo Nanoscale vol 4 no 13pp 3969ndash3976 2012

[33] M I Kim Y Ye M-A Woo J Lee and H G Park ldquoA highlyefficient colorimetric immunoassay using a nanocompositeentrapping magnetic and platinum nanoparticles in orderedmesoporous carbonrdquo Advanced Healthcare Materials vol 3 no1 pp 36ndash41 2014

[34] J Liu X Hu S Hou et al ldquoAuPt coreshell nanorods withperoxidase- and ascorbate oxidase-like activities for improveddetection of glucoserdquo Sensors and Actuators B Chemical vol166-167 pp 708ndash714 2012

[35] M I Kim M S Kim M-AWoo et al ldquoHighly efficient colori-metric detection of target cancer cells utilizing superior catalyticactivity of graphene oxide-magnetic-platinum nanohybridsrdquoNanoscale vol 6 no 3 pp 1529ndash1536 2014

[36] M Liu H Zhao S Chen H Yu and X Quan ldquoInterface engi-neering catalytic graphene for smart colorimetric biosensingrdquoACS Nano vol 6 no 4 pp 3142ndash3151 2012

[37] Y Ye T Kong X Yu YWu K Zhang and XWang ldquoEnhancednonenzymatic hydrogen peroxide sensing with reducedgraphene oxideferroferric oxide nanocompositesrdquo Talantavol 89 pp 417ndash421 2012

[38] R Cui Z Han and J-J Zhu ldquoHelical carbon nanotubesintrinsic peroxidase catalytic activity and its application forbiocatalysis and biosensingrdquo ChemistrymdashA European Journalvol 17 no 34 pp 9377ndash9384 2011

[39] M Liu H Zhao S Chen H Yu and X Quan ldquoStimuli-responsive peroxidase mimicking at a smart graphene inter-facerdquo Chemical Communications vol 48 no 56 pp 7055ndash70572012

[40] S Liu J Tian L Wang Y Luo and X Sun ldquoA general strategyfor the production of photoluminescent carbon nitride dotsfrom organic amines and their application as novel peroxidase-like catalysts for colorimetric detection of H

2O2and glucoserdquo

RSC Advances vol 2 no 2 pp 411ndash413 2012[41] F Qu T Li and M Yang ldquoColorimetric platform for visual

detection of cancer biomarker based on intrinsic peroxidaseactivity of graphene oxiderdquo Biosensors and Bioelectronics vol26 no 9 pp 3927ndash3931 2011

[42] W Shi QWang Y Long et al ldquoCarbon nanodots as peroxidasemimetics and their applications to glucose detectionrdquo ChemicalCommunications vol 47 no 23 pp 6695ndash6697 2011

[43] X Wang K Qu B Xu J Ren and X Qu ldquoMulticolorluminescent carbon nanoparticles synthesis supramolecularassembly with porphyrin intrinsic peroxidase-like catalyticactivity and applicationsrdquo Nano Research vol 4 no 9 pp 908ndash920 2011

[44] H Wei and E Wang ldquoFe3O4magnetic nanoparticles as per-

oxidase mimetics and their applications in H2O2and glucose

detectionrdquo Analytical Chemistry vol 80 no 6 pp 2250ndash22542008

[45] Q Chang KDeng L ZhuG Jiang C Yu andH Tang ldquoDeter-mination of hydrogen peroxide with the aid of peroxidase-like

10 Journal of Nanomaterials

Fe3O4magnetic nanoparticles as the catalystrdquo Microchimica

Acta vol 165 no 3-4 pp 299ndash305 2009[46] Z Jiang L Kun H Ouyang A Liang and H Jiang ldquoA simple

and sensitive fluorescence quenching method for the determi-nation of H

2O2using rhodamine B and Fe

3O4nanocatalystrdquo

Journal of Fluorescence vol 21 no 5 pp 2015ndash2020 2011[47] Y Jv B Li andR Cao ldquoPositively-charged gold nanoparticles as

peroxidiase mimic and their application in hydrogen peroxideand glucose detectionrdquo Chemical Communications vol 46 no42 pp 8017ndash8019 2010

[48] K Wang J-J Xu D-C Sun H Wei and X-H Xia ldquoSelectiveglucose detection based on the concept of electrochemicaldepletion of electroactive species in diffusion layerrdquo Biosensorsand Bioelectronics vol 20 no 7 pp 1366ndash1372 2005

[49] M I Kim Y Ye B Y Won S Shin J Lee and H G Park ldquoAhighly efficient electrochemical biosensing platform by employ-ing conductive nanocomposite entrapping magnetic nano-particles and oxidase in mesoporous carbon foamrdquo AdvancedFunctional Materials vol 21 no 15 pp 2868ndash2875 2011

[50] M I Kim J Shim T Li J Lee and H G Park ldquoFabrica-tion of nanoporous nanocomposites entrapping Fe

3O4mag-

netic nanoparticles and oxidases for colorimetric biosensingrdquoChemistrymdashAEuropean Journal vol 17 no 38 pp 10700ndash107072011

[51] M I Kim J Shim T Li et al ldquoColorimetric quantificationof galactose using a nanostructured multi-catalyst systementrapping galactose oxidase and magnetic nanoparticles asperoxidasemimeticsrdquoAnalyst vol 137 no 5 pp 1137ndash1143 2012

[52] M I Kim J Shim H J Parab S C Shin J Lee and H G ParkldquoA convenient alcohol sensor using one-pot nanocompositeentrapping alcohol oxidase and magnetic nanoparticles as per-oxidase mimeticsrdquo Journal of Nanoscience and Nanotechnologyvol 12 no 7 pp 5914ndash5919 2012

[53] K S Park M I Kim D-Y Cho and H G Park ldquoLabel-free colorimetric detection of nucleic acids based on target-induced shielding against the peroxidase-mimicking activity ofmagnetic nanoparticlesrdquo Small vol 7 no 11 pp 1521ndash1525 2011

[54] J A Brinkman M Z Rahmani W E Jones A K Chaturvediand M E Hagensee ldquoOptimization of PCR based detection ofhuman papillomavirus DNA from urine specimensrdquo Journal ofClinical Virology vol 29 no 4 pp 230ndash240 2004

[55] L Hafner K Beagley and P Timms ldquoChlamydia trachomatisinfection host immune responses and potential vaccinesrdquoMucosal Immunology vol 1 no 2 pp 116ndash130 2008

[56] M I Kim K S Park and H G Park ldquoUltrafast colorimetricdetection of nucleic acids based on the inhibition of the oxidaseactivity of cerium oxide nanoparticlesrdquo Chemical Communica-tions vol 50 no 67 pp 9577ndash9580 2014

[57] Z Zhang Z Wang X Wang and X Yang ldquoMagneticnanoparticle-linked colorimetric aptasensor for the detection ofthrombinrdquo Sensors and Actuators B Chemical vol 147 no 2 pp428ndash433 2010

[58] B W Blais and A Martinez-Perez ldquoDetection of groupD salmonellae including Salmonella enteritidis in eggs bypolymyxin-based enzyme-linked immunosorbent assayrdquo Jour-nal of Food Protection vol 71 no 2 pp 392ndash396 2008

[59] V Tripathi S Nara S K Chaube et al ldquoDevelopment ofrapid and sensitive one-step direct enzyme linked immunosor-bent assay for 17-120572-OH-progesterone in serumrdquo Journal ofImmunoassay and Immunochemistry vol 29 no 2 pp 117ndash1272008

[60] K DMcReynolds M J Hadd and J Gervay-Hague ldquoSynthesisof biotinylated glycoconjugates and their use in a novel ELISAfor direct comparison ofHIV-1 gp120 recognition ofGalCer andrelated carbohydrate analoguesrdquo Bioconjugate Chemistry vol10 no 6 pp 1021ndash1031 1999

[61] H Hocini S Iscaki J-P Bouvet M D Kazatchkine and LBelec ldquoAn ELISA method to measure total and specific humansecretory IgA subclasses based on selective degradation by IgA1-proteaserdquo Journal of Immunological Methods vol 235 no 1-2pp 53ndash60 2000

[62] L Micheli S Di Stefano D Moscone et al ldquoProduction ofantibodies and development of highly sensitive formats ofenzyme immunoassay for saxitoxin analysisrdquo Analytical andBioanalytical Chemistry vol 373 no 8 pp 678ndash684 2002

[63] L Gao J Wu S Lyle K Zehr L Cao and D Gao ldquoMagnetitenanoparticle-linked immunosorbent assayrdquo Journal of PhysicalChemistry C vol 112 no 44 pp 17357ndash17361 2008

[64] X-Q Zhang S-W Gong Y Zhang T Yang C-YWang andNGu ldquoPrussian blue modified iron oxide magnetic nanoparticlesand their high peroxidase-like activityrdquo Journal of MaterialsChemistry vol 20 no 24 pp 5110ndash5116 2010

[65] Z Tang H Wu Y Zhang Z Li and Y Lin ldquoEnzyme-mimicactivity of ferric nano-core residing in ferritin and its biosensingapplicationsrdquo Analytical Chemistry vol 83 no 22 pp 8611ndash8616 2011

[66] M-A Woo M I Kim J H Jung K S Park T S Seoand H G Park ldquoA novel colorimetric immunoassay utilizingthe peroxidase mimicking activity of magnetic nanoparticlesrdquoInternational Journal of Molecular Sciences vol 14 no 5 pp9999ndash10014 2013

[67] V H C Bramwell G S Doig A B Tuck et al ldquoChangesover time of extracellular domain of HER2 (ECDHER2) serumlevels have prognostic value in metastatic breast cancerrdquo BreastCancer Research andTreatment vol 114 no 3 pp 503ndash511 2009

[68] K S Asgeirsson A Agrawal C Allen et al ldquoSerum epidermalgrowth factor receptor and HER2 expression in primary andmetastatic breast cancer patientsrdquo Breast Cancer Research vol9 no 6 article R75 2007

[69] A Asati C Kaittanis S Santra and J M Perez ldquoPH-tunableoxidase-like activity of cerium oxide nanoparticles achievingsensitive fluorigenic detection of cancer biomarkers at neutralpHrdquo Analytical Chemistry vol 83 no 7 pp 2547ndash2553 2011

[70] K L Fan C Q Cao Y X Pan et al ldquoMagnetoferritinnanoparticles for targeting and visualizing tumour tissuesrdquoNature Nanotechnology vol 7 no 7 pp 459ndash464 2012

[71] S Beatty H-H Koh M Phil D Henson and M BoultonldquoThe role of oxidative stress in the pathogenesis of age-relatedmacular degenerationrdquo Survey of Ophthalmology vol 45 no 2pp 115ndash134 2000

[72] C Korsvik S Patil S Seal and W T Self ldquoSuperoxidedismutase mimetic properties exhibited by vacancy engineeredceria nanoparticlesrdquo Chemical Communications no 10 pp1056ndash1058 2007

[73] E G Heckert A S Karakoti S Seal andW T Self ldquoThe role ofcerium redox state in the SOD mimetic activity of nanoceriardquoBiomaterials vol 29 no 18 pp 2705ndash2709 2008

[74] J Chen S Patil S Seal and J F McGinnis ldquoRare earthnanoparticles prevent retinal degeneration induced by intracel-lular peroxidesrdquo Nature Nanotechnology vol 1 no 2 pp 142ndash150 2006

Journal of Nanomaterials 11

[75] S M Hirst A S Karakoti R D Tyler N Sriranganathan SSeal and C M Reilly ldquoAnti-inflammatory properties of ceriumoxide nanoparticlesrdquo Small vol 5 no 24 pp 2848ndash2856 2009

[76] D-M Huang J-K Hsiao Y-C Chen et al ldquoThe promotion ofhuman mesenchymal stem cell proliferation by superparamag-netic iron oxide nanoparticlesrdquo Biomaterials vol 30 no 22 pp3645ndash3651 2009

[77] N Ding N Yan C Ren and X Chen ldquoColorimetric determi-nation of melamine in dairy products by Fe

3O4Magnetic nano-

particles-H2O2-ABTS detection systemrdquo Analytical Chemistry

vol 82 no 13 pp 5897ndash5899 2010[78] J Zhang J Zhuang L Gao et al ldquoDecomposing phenol by the

hidden talent of ferromagnetic nanoparticlesrdquo Chemospherevol 73 no 9 pp 1524ndash1528 2008

[79] J Z Jiang J Zou L H Zhu L Huang H Jiang and YZhang ldquoDegradation of methylene blue with H

2O2activated

by peroxidase-like Fe3O4magnetic nanoparticlesrdquo Journal of

Nanoscience and Nanotechnology vol 11 no 6 pp 4793ndash47992011

[80] L Gao K M Giglio J L Nelson H Sondermann and AJ Travis ldquoFerromagnetic nanoparticles with peroxidase-likeactivity enhance the cleavage of biological macromolecules forbiofilm eliminationrdquo Nanoscale vol 6 no 5 pp 2588ndash25932014

[81] K Vickery A Pajkos and Y Cossart ldquoRemoval of biofilmfrom endoscopes evaluation of detergent efficiencyrdquo AmericanJournal of Infection Control vol 32 no 3 pp 170ndash176 2004

Submit your manuscripts athttpwwwhindawicom

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CorrosionInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Polymer ScienceInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CeramicsJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Biomaterials

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Journal ofNanomaterials

Page 6: Review Article Recent Research Trends and Future …downloads.hindawi.com/journals/jnm/2015/756278.pdfnovel biosensor, immunoassay, cancer diagnostics, therapeutics, and environmental

6 Journal of Nanomaterials

nanoceria as an oxidase mimic made detection of tumorcells easier than with traditional immunoassay because itdirectly oxidized a colorimetric substrate to a colored productwithout H

2O2and additional steps to introduce an enzyme-

conjugated secondary antibody Further advances in thistechnology were also reported by employing a fluorescence-generating substrate ampliflu to detect target cancer cells ataround neutral pH [69]

Another interesting study to visualize target tumor tissueswithout the use of any additional targeting ligands hasalso been described [70] In this study peroxidase-like ironoxide nanoparticles were encapsulated inside a recombinanthuman heavy-chain ferritin (Hfn) protein shell which bindsto tumor cells that overexpress transferrin receptor 1The ironoxide cores catalyzed the oxidation of peroxidase substratesin the presence of H

2O2to produce the colorimetric signal

that was used to visualize tumor tissues Through thisstrategy nine types of cancer were successfully verified withenough specificity and sensitivity

34 Therapeutic Applications As described above nano-zymes have been widely used for detection and diagnos-tic methods Besides these applications many researchershave also studied therapeutic applications including anti-inflammatory effects neuroprotection stem cell growth andantiaging In general SOD was often utilized for therapeuticapplications owing to its protective role as a scavenger of reac-tive oxygen intermediates (ROIs) Intracellular concentrationof ROI including hydrogen peroxidase hypochlorite ionshydroxyl radicals hydroxyl ions and superoxide anions hasbeen known to be a cause of cell degeneration and associateddiseases [71] Inspired by earlier studies by Seal et al whichrevealed the activity of CeO

2NPs as a SOD-mimic [72 73]

various studies have been attempted to develop SOD-mimicking nanozymes

Chen at al reported that nanoceria as a SOD-mimicprevented retinal degeneration by inhibiting the productionof ROIs [74] In their work nanoceria prevented ROI-induced apoptosis and intracellular accumulation of ROIin cultured retinal neurons in the presence of H

2O2 They

further demonstrated that nanoceria injected into the eyes ofrats protected retina photoreceptor cells from light-induceddegeneration The study by Hirst et al also demonstratedthat nanoceria could be used for anti-inflammation byelimination of the radical oxygen species in J774A1 murinemacrophage cells [75]

Superparamagnetic iron oxide (SPIO) nanoparticles havebeen employed to promote growth of stem cells Huanget al reported that Ferucarbotran a commercialized SPIOcould promote cell growth in humanmesenchymal stem cells(hMSCs) by diminishing intracellular H

2O2and also accel-

erate cell cycle progression [76] In this report the intrinsicperoxidase-like activity of SPIO dramatically reduced intra-cellular H

2O2after internalization into hMSCs as well as

free iron ions released from lysosomal degradation of SPIO-affected cell cycle control molecules

35 Environmental Engineering Recently environmentalproblems such as water and air pollution food safety and

public health have become growing concerns in societyIn addition to the aforementioned applications nanozyme-based techniques have been explored for use in the field ofenvironmental technology

351 Pollutant Detection Ding et al developed a simpleand rapid colorimetric method for detecting melamine anorganic nitrogenous compound which is toxic when swal-lowed and has been illegally added to dairy products [77]The principle of this method is as follows Melamine inhibitsthe catalytic oxidation of colorimetric substrates (ABTS) byMNPs in the presence of H

2O2 because it competitively

reacts with H2O2 forming an additional compound Conse-

quently the intensity of the ABTS color signal was dependenton the concentration of melamine On the basis of thisreaction a colorimetric systemusingMNPs could enable easydetection by the naked eye of concentrations of melamineabove safety limits in dairy products

Nanocomposite-entrapping MNPs and oxidase in meso-porous carbonwere used to detect several phenol compoundsamperometrically such as phenol cresol and cathechol[49] These phenol compounds produced a concentration-dependent increase of cathodic current in this system whichmay have great potential in the field of environmentalmonitoring

352 Pollutant Removal Although there have been manymethods for removal of industrial dyestuffs such as absorp-tion precipitation and ultrasonic decomposition they couldnot efficiently degrade organic pollutants in wastewaterNanozyme-based methods have been found to be a power-ful cost-effective and simple method for degradation andmineralization of organic dyes from industrial processesMost prominently MNPs such as peroxidase have beeninvestigated for degradation of organic pollutants such asmethylene blue phenol and rhodamine B A MNP-baseddegradation method offers distinct advantages over existingdegradation methods which use HRP such as lower costhigh stability and reusability MNPs-H

2O2could remove

85 of phenol from aqueous solution within three hours[78] The MNPs-based degradation showed higher efficiencycompared to HRP-based degradation and stability in a broadrange of temperatures (5ndash90∘C) leading to ease of storageFurthermore MNPs could be captured by the application ofan external field and recycled for five rounds retaining almost100 of their activity Removal of methylene blue by MNPs-H2O2coupled method has also been successfully performed

by Jiang et al [79] It was observed that 96ofmethylene bluewas degraded in 15 minutes at optimized condition

Gao et al reported that MNPs-H2O2system could

degrade biofilm and kill resident bacteria [80] Biofilm espe-cially formed by Pseudomonas aeruginosa occurs in hospitalwater systems and medical devices with high frequencybecoming a common cause of nosocomial infection [81]In this report MNPs-H

2O2system exhibited significantly

higher efficiency than the use of H2O2in degradation of

biofilm The authors confirmed that additional free hydroxylradicals generated by MNP catalysis of H

2O2facilitated

the oxidative cleavage of biofilm components (nucleic acids

Journal of Nanomaterials 7

Table1Va

rious

applicationstu

dies

basedon

nano

zymes

Applicationfield

Nanozym

esAc

tivity

Detectio

nmetho

dDetails

Ref

Biosensor

MNPs

Peroxidase

Colorim

etric

H2O2biosensor

[9]

AuNPs

Glucose

oxidase

Colorim

etric

Nucleicacid

detection

[15]

Carboxyl-m

odified

graphene

oxide

Peroxidase

Colorim

etric

H2O2andglucoseb

iosensor

[23]

MNPs

Peroxidase

Colorim

etric

H2O2andglucoseb

iosensor

[44]

MNPs

Peroxidase

Colorim

etric

H2O2biosensor

[45]

MNPs

Peroxidase

Colorim

etric

H2O2biosensor

[46]

AuNPs

Peroxidase

Colorim

etric

H2O2andglucoseb

iosensor

[47]

MNPs

Peroxidase

Electro

chem

ical

Glucose

biosensor

[48]

MNPs

(with

oxidaseinmesop

orou

scarbo

n)Peroxidase

Electro

chem

ical

Glucose

biosensor

[49]

MNPs

(with

oxidaseinmesop

orou

ssilica)

Peroxidase

Colorim

etric

Glucose

andcholesterolbiosensor

[50]

MNPs

(with

oxidaseinmesop

orou

ssilica)

Peroxidase

Colorim

etric

Galactose

biosensor

[51]

MNPs

(with

oxidaseinmesop

orou

ssilica)

Peroxidase

Colorim

etric

Alcoh

olbiosensor

[52]

MNPs

Peroxidase

Colorim

etric

Nucleicacid

detection(Chlam

ydiatra

chom

atis)

[53]

CeO2NPs

Oxidase

Colorim

etric

Nucleicacid

detection(Chlam

ydiatra

chom

atis)

[56]

Chito

san-mod

ified

MNPs

with

thrombinaptamers

Peroxidase

Colorim

etric

Thrombindetection

[57]

Immun

oassay

MNPs

Peroxidase

Colorim

etric

Cardiactropo

ninI(Tn

I)detection

[9]

MNPs-PtN

Psin

mesop

orou

scarbo

nPeroxidase

Colorim

etric

Rotavirusa

ndHER

2detection

[33]

Graph

eneo

xide

Peroxidase

Colorim

etric

Prostatespecifica

ntigen

(PSA

)detectio

n[41]

Chito

san-mod

ified

MNPs

Peroxidase

Colorim

etric

Mou

seIgGandcarcinoembryonica

ntigen

detection

[63]

Prussia

nblue

mod

ified120574-Fe 2O3NPs

Peroxidase

Colorim

etric

IgGdetection

[64]

Ferritins

Peroxidase

Fluo

rometric

Avidin

andhu

man

ceruloplasmin

detection

[65]

MNPs

Peroxidase

Colorim

etric

Rotavirusa

ndHER

2detection

[66]

MNPs-PtN

Pson

graphene

oxide

Peroxidase

Colorim

etric

fluo

rometric

HER

2detectionandim

aging

[35]

Cancer

diagno

stics

(with

outimmun

ereactio

n)andtherapy

Poly(acrylicacid)-coated

CeO2NPs

Oxidase

Colorim

etric

Lung

cancer

celldetection

[13]

Poly(acrylicacid)-coated

CeO2NPs

Oxidase

Colorim

etric

Lung

andbreastcancer

celldetection

[69]

MagnetoferritinNPs

Peroxidase

Colorim

etric

fluo

rometric

Cancer

cellim

aging

[70]

CeO2NPs

Superoxide

dism

utase

Preventio

nof

retin

aldegeneratio

n[74]

CeO2NPs

Superoxide

dism

utase

Anti-infl

ammation

[75]

Superparam

agnetic

ironoxideN

PsPeroxidase

Prom

otionof

stem

cellgrow

th[76]

Environm

ental

engineering

MNPs

(with

oxidaseinmesop

orou

scarbo

n)Peroxidase

Electro

chem

ical

Phenolcresolandcathecho

ldetectio

n[49]

MNPs

Peroxidase

Colorim

etric

Mela

mined

etectio

n[77]

MNPs

Peroxidase

Removalof

phenol

[78]

MNPs

Peroxidase

Removalof

methylene

blue

[79]

MNPs

Peroxidase

Biofi

lmdegradation

[80]

8 Journal of Nanomaterials

proteins and polysaccharides) as well as killing residentbacteria

4 Conclusions and Future Research Aspects

Nanozymes have recently emerged as a potent alternativeto natural enzymes As discussed above although they arestill in the initial stages of research their use has developedsubstantially inmanydifferent detection and treatmentmeth-ods for biomolecules (Table 1) Despite the advantages ofnanozymes such as their low cost high stability robustnessease of mass production and long-term storability thereare several challenges to be tackled for practical use Firstlymost nanozymes have low activity compared to naturalenzymes Even if the nanomaterial itself is highly activeadditional coating and surface modification can decrease itsperformance Therefore development of novel nanozymesexhibiting high activity and appropriate surface-modificationtechniques are the emerging issues in the field of nanozymesNanozymes also have low selectivity to targets owing to theabsence of active sites where a substrate molecule binds andundergoes a chemical reaction in a natural enzyme Althoughresearchers have designed various types of surface-modifiednanozymes with polymers nucleic acids and antibodiesto provide selectivity mimicking natural enzymes this isstill insufficient for use in practical applications Toxicity ofnanozymes to humans and the ecosystem is also an essentialissue to be solved in regard to environmental and therapeuticapplications

In order for nanozymes to be positioned as a novelsource technology by efficiently overcoming the limitationsof natural enzymes we offer the following suggestions Thedevelopment of new nanozymes with higher activity andother positive properties than existing nanozymes is requiredWhile traditional research on developing nanozymes hasbeen performed by random screening of the enzyme-like activities of existing unspecified nanomaterials futureresearch will follow a strategy of rational screening ofenzyme-like activity based on those atomic compositionswhich are envisaged to catalyze enzymatic reactions Fur-thermore a strategy to prepare composites can be expectedto resolve the current major limitations of nanozymes oflow catalytic activity by exploiting their synergistic effectto facilitate electron transfer between composite materialsduring redox reaction Bioinspired synthesis of nanozymesalso provides an option to prepare nontoxic nanozymesby effectively circumventing the use of toxic chemicals inconventional chemical synthesis thereby accelerating theiruse in therapeutic applications Finally the developmentof novel surface engineering technology that can makenanozymes selective to target substrates will be importantin this field With the abovementioned research projects weexpect nanozymes to be widely employed in a wide range ofapplications in the near future

Conflict of Interests

The authors declare no financial or commercial conflict ofinterests

Acknowledgments

This work was supported by the Basic Science ResearchProgram through theNational Research Foundation of Korea(NRF) funded by the Ministry of Science ICT amp FuturePlanning (NRF-2014R1A1A1006016) and by the Gachon Uni-versity research fund of 2014 (GCU-2014-0110)

References

[1] D L Nelson and M M Cox Lehninger Principles of Biochem-istry vol 6 chapter 6 W H Freeman New York NY USA2005

[2] Z Liu R Cai L Mao H Huang and W Ma ldquoHighly sensitivespectrofluorimetric determination of hydrogen peroxide with120573-cyclodextrin-hemin as catalystrdquo Analyst vol 124 no 2 pp173ndash176 1999

[3] R P Bonar-Law and J K M Sanders ldquoPolyol recognition bya steroid-capped porphyrin Enhancement and modulation ofmisfit guest binding by added water or methanolrdquo Journal of theAmerican Chemical Society vol 117 no 1 pp 259ndash271 1995

[4] X-M Huang M Zhu L-Y Mao and H-X Shen ldquoCat-alytic determination of hydrogen peroxide by using themolybdenum-porphyrin complex as a mimetic enzyme ofperoxidaserdquo Analytical Sciences vol 13 no 1 pp 145ndash147 1997

[5] L Fruk andCMNiemeyer ldquoCovalent hemin-DNAadducts forgenerating a novel class of artificial heme enzymesrdquoAngewandteChemiemdashInternational Edition vol 44 no 17 pp 2603ndash26062005

[6] Q Wang Z Yang X Zhang X Xiao C K Chang and B XuldquoA supramolecular-hydrogel-encapsulated hemin as an artifi-cial enzyme to mimic peroxidaserdquo Angewandte Chemie Inter-national Edition vol 46 no 23 pp 4285ndash4289 2007

[7] Z Genfa and P K Dasgupta ldquoHematin as a peroxidase sub-stitute in hydrogen peroxide determinationsrdquo Analytical Chem-istry vol 64 no 5 pp 517ndash522 1992

[8] H Wei and E Wang ldquoNanomaterials with enzyme-like char-acteristics (nanozymes) next-generation artificial enzymesrdquoChemical Society Reviews vol 42 no 14 pp 6060ndash6093 2013

[9] L Gao J Zhuang LNie et al ldquoIntrinsic peroxidase-like activityof ferromagnetic nanoparticlesrdquo Nature Nanotechnology vol 2no 9 pp 577ndash583 2007

[10] R Polsky R Gill L Kaganovsky and I Willner ldquoNucleic acid-functionalized Pt nanoparticles catalytic labels for the ampli-fied electrochemical detection of biomoleculesrdquo AnalyticalChemistry vol 78 no 7 pp 2268ndash2271 2006

[11] T Li Y Du and E Wang ldquoPolyethyleneimine-functionalizedplatinum nanoparticles with high electrochemiluminescenceactivity and their applications to amplified analysis of bio-moleculesrdquo ChemistrymdashAn Asian Journal vol 3 no 11 pp1942ndash1948 2008

[12] W W He Y Liu J S Yuan et al ldquoAuPt nanostructures asoxidase and peroxidase mimetics for use in immunoassaysrdquoBiomaterials vol 32 no 4 pp 1139ndash1147 2011

[13] A Asati S Santra C Kaittanis S Nath and J M PerezldquoOxidase-like activity of polymer-coated cerium oxide nano-partielesrdquo Angewandte ChemiemdashInternational Edition vol 48no 13 pp 2308ndash2312 2009

[14] W J Luo C F Zhu S Su et al ldquoSelf-catalyzed self-limitinggrowth of glucose oxidase-mimicking gold nanoparticlesrdquo ACSNano vol 4 no 12 pp 7451ndash7458 2010

Journal of Nanomaterials 9

[15] X Zheng Q Liu C Jing et al ldquoCatalytic gold nanoparticles fornanoplasmonic detection of DNA hybridizationrdquo AngewandteChemie International Edition vol 50 no 50 pp 11994ndash119982011

[16] Y J Long Y F Li Y Liu J J Zheng J Tang and C JHuang ldquoVisual observation of the mercury-stimulated peroxi-dase mimetic activity of gold nanoparticlesrdquo Chemical Commu-nications vol 47 no 43 pp 11939ndash11941 2011

[17] W Chen J Chen Y-B Feng et al ldquoPeroxidase-like activityof water-soluble cupric oxide nanoparticles and its analyticalapplication for detection of hydrogen peroxide and glucoserdquoAnalyst vol 137 no 7 pp 1706ndash1712 2012

[18] W Luo Y-S Li J Yuan et al ldquoUltrasensitive fluorometricdetermination of hydrogen peroxide and glucose by usingmultiferroic BiFeO

3nanoparticles as a catalystrdquo Talanta vol 81

no 3 pp 901ndash907 2010[19] S H He W B Shi X D Zhang J A Li and Y M Huang ldquo120573-

Cyclodextrins-based inclusion complexes of CoFe2O4magnetic

nanoparticles as catalyst for the luminol chemiluminescencesystem and their applications in hydrogen peroxide detectionrdquoTalanta vol 82 no 1 pp 377ndash383 2010

[20] W B Shi X D Zhang S H He and Y M Huang ldquoCoFe2O4

magnetic nanoparticles as a peroxidasemimicmediated chemi-luminescence for hydrogen peroxide and glucoserdquo ChemicalCommunications vol 47 no 38 pp 10785ndash10787 2011

[21] Y W Fan and Y M Huang ldquoThe effective peroxidase-likeactivity of chitosan-functionalized CoFe

2O4nanoparticles for

chemiluminescence sensing of hydrogen peroxide and glucoserdquoAnalyst vol 137 no 5 pp 1225ndash1231 2012

[22] A K Dutta S K Maji D N Srivastava et al ldquoSynthesis ofFeS and FeSe nanoparticles from a single source precursor astudy of their photocatalytic activity peroxidase-like behaviorand electrochemical sensing of H

2O2rdquo ACS Applied Materials

and Interfaces vol 4 no 4 pp 1919ndash1927 2012[23] Y Song K Qu C Zhao J Ren and X Qu ldquoGraphene oxide

intrinsic peroxidase catalytic activity and its application toglucose detectionrdquoAdvancedMaterials vol 22 no 19 pp 2206ndash2210 2010

[24] Y Song X Wang C Zhao K Qu J Ren and X Qu ldquoLabel-free colorimetric detection of single nucleotide polymorphismby using single-walled carbon nanotube intrinsic peroxidase-like activityrdquo ChemistrymdashA European Journal vol 16 no 12 pp3617ndash3621 2010

[25] Y Guo J Li and S Dong ldquoHemin functionalized graphenenanosheets-based dual biosensor platforms for hydrogen per-oxide and glucoserdquo Sensors and Actuators B Chemical vol 160no 1 pp 295ndash300 2011

[26] J Xie X Zhang H Wang H Zheng Y Huang and J XieldquoAnalytical and environmental applications of nanoparticles asenzyme mimeticsrdquo TrACmdashTrends in Analytical Chemistry vol39 pp 114ndash129 2012

[27] A K Gupta and M Gupta ldquoSynthesis and surface engineeringof iron oxide nanoparticles for biomedical applicationsrdquoBioma-terials vol 26 no 18 pp 3995ndash4021 2005

[28] J Mu Y Wang M Zhao and L Zhang ldquoIntrinsic peroxidase-like activity and catalase-like activity of Co

3O4nanoparticlesrdquo

Chemical Communications vol 48 no 19 pp 2540ndash2542 2012[29] Y Wan P Qi D Zhang J Wu and Y Wang ldquoMan-

ganese oxide nanowire-mediated enzyme-linked immunosor-bent assayrdquo Biosensors and Bioelectronics vol 33 no 1 pp 69ndash74 2012

[30] R Andre F Natalio M Humanes et al ldquoV2O5nanowires

with an intrinsic peroxidase-like activityrdquo Advanced FunctionalMaterials vol 21 no 3 pp 501ndash509 2011

[31] W Chen J Chen A-L Liu L-M Wang G-W Li and X-H Lin ldquoPeroxidase-like activity of cupric oxide nanoparticlerdquoChemCatChem vol 3 no 7 pp 1151ndash1154 2011

[32] Y-L DongH-G Zhang Z U Rahman et al ldquoGraphene oxide-Fe3O4magnetic nanocomposites with peroxidase-like activity

for colorimetric detection of glucoserdquo Nanoscale vol 4 no 13pp 3969ndash3976 2012

[33] M I Kim Y Ye M-A Woo J Lee and H G Park ldquoA highlyefficient colorimetric immunoassay using a nanocompositeentrapping magnetic and platinum nanoparticles in orderedmesoporous carbonrdquo Advanced Healthcare Materials vol 3 no1 pp 36ndash41 2014

[34] J Liu X Hu S Hou et al ldquoAuPt coreshell nanorods withperoxidase- and ascorbate oxidase-like activities for improveddetection of glucoserdquo Sensors and Actuators B Chemical vol166-167 pp 708ndash714 2012

[35] M I Kim M S Kim M-AWoo et al ldquoHighly efficient colori-metric detection of target cancer cells utilizing superior catalyticactivity of graphene oxide-magnetic-platinum nanohybridsrdquoNanoscale vol 6 no 3 pp 1529ndash1536 2014

[36] M Liu H Zhao S Chen H Yu and X Quan ldquoInterface engi-neering catalytic graphene for smart colorimetric biosensingrdquoACS Nano vol 6 no 4 pp 3142ndash3151 2012

[37] Y Ye T Kong X Yu YWu K Zhang and XWang ldquoEnhancednonenzymatic hydrogen peroxide sensing with reducedgraphene oxideferroferric oxide nanocompositesrdquo Talantavol 89 pp 417ndash421 2012

[38] R Cui Z Han and J-J Zhu ldquoHelical carbon nanotubesintrinsic peroxidase catalytic activity and its application forbiocatalysis and biosensingrdquo ChemistrymdashA European Journalvol 17 no 34 pp 9377ndash9384 2011

[39] M Liu H Zhao S Chen H Yu and X Quan ldquoStimuli-responsive peroxidase mimicking at a smart graphene inter-facerdquo Chemical Communications vol 48 no 56 pp 7055ndash70572012

[40] S Liu J Tian L Wang Y Luo and X Sun ldquoA general strategyfor the production of photoluminescent carbon nitride dotsfrom organic amines and their application as novel peroxidase-like catalysts for colorimetric detection of H

2O2and glucoserdquo

RSC Advances vol 2 no 2 pp 411ndash413 2012[41] F Qu T Li and M Yang ldquoColorimetric platform for visual

detection of cancer biomarker based on intrinsic peroxidaseactivity of graphene oxiderdquo Biosensors and Bioelectronics vol26 no 9 pp 3927ndash3931 2011

[42] W Shi QWang Y Long et al ldquoCarbon nanodots as peroxidasemimetics and their applications to glucose detectionrdquo ChemicalCommunications vol 47 no 23 pp 6695ndash6697 2011

[43] X Wang K Qu B Xu J Ren and X Qu ldquoMulticolorluminescent carbon nanoparticles synthesis supramolecularassembly with porphyrin intrinsic peroxidase-like catalyticactivity and applicationsrdquo Nano Research vol 4 no 9 pp 908ndash920 2011

[44] H Wei and E Wang ldquoFe3O4magnetic nanoparticles as per-

oxidase mimetics and their applications in H2O2and glucose

detectionrdquo Analytical Chemistry vol 80 no 6 pp 2250ndash22542008

[45] Q Chang KDeng L ZhuG Jiang C Yu andH Tang ldquoDeter-mination of hydrogen peroxide with the aid of peroxidase-like

10 Journal of Nanomaterials

Fe3O4magnetic nanoparticles as the catalystrdquo Microchimica

Acta vol 165 no 3-4 pp 299ndash305 2009[46] Z Jiang L Kun H Ouyang A Liang and H Jiang ldquoA simple

and sensitive fluorescence quenching method for the determi-nation of H

2O2using rhodamine B and Fe

3O4nanocatalystrdquo

Journal of Fluorescence vol 21 no 5 pp 2015ndash2020 2011[47] Y Jv B Li andR Cao ldquoPositively-charged gold nanoparticles as

peroxidiase mimic and their application in hydrogen peroxideand glucose detectionrdquo Chemical Communications vol 46 no42 pp 8017ndash8019 2010

[48] K Wang J-J Xu D-C Sun H Wei and X-H Xia ldquoSelectiveglucose detection based on the concept of electrochemicaldepletion of electroactive species in diffusion layerrdquo Biosensorsand Bioelectronics vol 20 no 7 pp 1366ndash1372 2005

[49] M I Kim Y Ye B Y Won S Shin J Lee and H G Park ldquoAhighly efficient electrochemical biosensing platform by employ-ing conductive nanocomposite entrapping magnetic nano-particles and oxidase in mesoporous carbon foamrdquo AdvancedFunctional Materials vol 21 no 15 pp 2868ndash2875 2011

[50] M I Kim J Shim T Li J Lee and H G Park ldquoFabrica-tion of nanoporous nanocomposites entrapping Fe

3O4mag-

netic nanoparticles and oxidases for colorimetric biosensingrdquoChemistrymdashAEuropean Journal vol 17 no 38 pp 10700ndash107072011

[51] M I Kim J Shim T Li et al ldquoColorimetric quantificationof galactose using a nanostructured multi-catalyst systementrapping galactose oxidase and magnetic nanoparticles asperoxidasemimeticsrdquoAnalyst vol 137 no 5 pp 1137ndash1143 2012

[52] M I Kim J Shim H J Parab S C Shin J Lee and H G ParkldquoA convenient alcohol sensor using one-pot nanocompositeentrapping alcohol oxidase and magnetic nanoparticles as per-oxidase mimeticsrdquo Journal of Nanoscience and Nanotechnologyvol 12 no 7 pp 5914ndash5919 2012

[53] K S Park M I Kim D-Y Cho and H G Park ldquoLabel-free colorimetric detection of nucleic acids based on target-induced shielding against the peroxidase-mimicking activity ofmagnetic nanoparticlesrdquo Small vol 7 no 11 pp 1521ndash1525 2011

[54] J A Brinkman M Z Rahmani W E Jones A K Chaturvediand M E Hagensee ldquoOptimization of PCR based detection ofhuman papillomavirus DNA from urine specimensrdquo Journal ofClinical Virology vol 29 no 4 pp 230ndash240 2004

[55] L Hafner K Beagley and P Timms ldquoChlamydia trachomatisinfection host immune responses and potential vaccinesrdquoMucosal Immunology vol 1 no 2 pp 116ndash130 2008

[56] M I Kim K S Park and H G Park ldquoUltrafast colorimetricdetection of nucleic acids based on the inhibition of the oxidaseactivity of cerium oxide nanoparticlesrdquo Chemical Communica-tions vol 50 no 67 pp 9577ndash9580 2014

[57] Z Zhang Z Wang X Wang and X Yang ldquoMagneticnanoparticle-linked colorimetric aptasensor for the detection ofthrombinrdquo Sensors and Actuators B Chemical vol 147 no 2 pp428ndash433 2010

[58] B W Blais and A Martinez-Perez ldquoDetection of groupD salmonellae including Salmonella enteritidis in eggs bypolymyxin-based enzyme-linked immunosorbent assayrdquo Jour-nal of Food Protection vol 71 no 2 pp 392ndash396 2008

[59] V Tripathi S Nara S K Chaube et al ldquoDevelopment ofrapid and sensitive one-step direct enzyme linked immunosor-bent assay for 17-120572-OH-progesterone in serumrdquo Journal ofImmunoassay and Immunochemistry vol 29 no 2 pp 117ndash1272008

[60] K DMcReynolds M J Hadd and J Gervay-Hague ldquoSynthesisof biotinylated glycoconjugates and their use in a novel ELISAfor direct comparison ofHIV-1 gp120 recognition ofGalCer andrelated carbohydrate analoguesrdquo Bioconjugate Chemistry vol10 no 6 pp 1021ndash1031 1999

[61] H Hocini S Iscaki J-P Bouvet M D Kazatchkine and LBelec ldquoAn ELISA method to measure total and specific humansecretory IgA subclasses based on selective degradation by IgA1-proteaserdquo Journal of Immunological Methods vol 235 no 1-2pp 53ndash60 2000

[62] L Micheli S Di Stefano D Moscone et al ldquoProduction ofantibodies and development of highly sensitive formats ofenzyme immunoassay for saxitoxin analysisrdquo Analytical andBioanalytical Chemistry vol 373 no 8 pp 678ndash684 2002

[63] L Gao J Wu S Lyle K Zehr L Cao and D Gao ldquoMagnetitenanoparticle-linked immunosorbent assayrdquo Journal of PhysicalChemistry C vol 112 no 44 pp 17357ndash17361 2008

[64] X-Q Zhang S-W Gong Y Zhang T Yang C-YWang andNGu ldquoPrussian blue modified iron oxide magnetic nanoparticlesand their high peroxidase-like activityrdquo Journal of MaterialsChemistry vol 20 no 24 pp 5110ndash5116 2010

[65] Z Tang H Wu Y Zhang Z Li and Y Lin ldquoEnzyme-mimicactivity of ferric nano-core residing in ferritin and its biosensingapplicationsrdquo Analytical Chemistry vol 83 no 22 pp 8611ndash8616 2011

[66] M-A Woo M I Kim J H Jung K S Park T S Seoand H G Park ldquoA novel colorimetric immunoassay utilizingthe peroxidase mimicking activity of magnetic nanoparticlesrdquoInternational Journal of Molecular Sciences vol 14 no 5 pp9999ndash10014 2013

[67] V H C Bramwell G S Doig A B Tuck et al ldquoChangesover time of extracellular domain of HER2 (ECDHER2) serumlevels have prognostic value in metastatic breast cancerrdquo BreastCancer Research andTreatment vol 114 no 3 pp 503ndash511 2009

[68] K S Asgeirsson A Agrawal C Allen et al ldquoSerum epidermalgrowth factor receptor and HER2 expression in primary andmetastatic breast cancer patientsrdquo Breast Cancer Research vol9 no 6 article R75 2007

[69] A Asati C Kaittanis S Santra and J M Perez ldquoPH-tunableoxidase-like activity of cerium oxide nanoparticles achievingsensitive fluorigenic detection of cancer biomarkers at neutralpHrdquo Analytical Chemistry vol 83 no 7 pp 2547ndash2553 2011

[70] K L Fan C Q Cao Y X Pan et al ldquoMagnetoferritinnanoparticles for targeting and visualizing tumour tissuesrdquoNature Nanotechnology vol 7 no 7 pp 459ndash464 2012

[71] S Beatty H-H Koh M Phil D Henson and M BoultonldquoThe role of oxidative stress in the pathogenesis of age-relatedmacular degenerationrdquo Survey of Ophthalmology vol 45 no 2pp 115ndash134 2000

[72] C Korsvik S Patil S Seal and W T Self ldquoSuperoxidedismutase mimetic properties exhibited by vacancy engineeredceria nanoparticlesrdquo Chemical Communications no 10 pp1056ndash1058 2007

[73] E G Heckert A S Karakoti S Seal andW T Self ldquoThe role ofcerium redox state in the SOD mimetic activity of nanoceriardquoBiomaterials vol 29 no 18 pp 2705ndash2709 2008

[74] J Chen S Patil S Seal and J F McGinnis ldquoRare earthnanoparticles prevent retinal degeneration induced by intracel-lular peroxidesrdquo Nature Nanotechnology vol 1 no 2 pp 142ndash150 2006

Journal of Nanomaterials 11

[75] S M Hirst A S Karakoti R D Tyler N Sriranganathan SSeal and C M Reilly ldquoAnti-inflammatory properties of ceriumoxide nanoparticlesrdquo Small vol 5 no 24 pp 2848ndash2856 2009

[76] D-M Huang J-K Hsiao Y-C Chen et al ldquoThe promotion ofhuman mesenchymal stem cell proliferation by superparamag-netic iron oxide nanoparticlesrdquo Biomaterials vol 30 no 22 pp3645ndash3651 2009

[77] N Ding N Yan C Ren and X Chen ldquoColorimetric determi-nation of melamine in dairy products by Fe

3O4Magnetic nano-

particles-H2O2-ABTS detection systemrdquo Analytical Chemistry

vol 82 no 13 pp 5897ndash5899 2010[78] J Zhang J Zhuang L Gao et al ldquoDecomposing phenol by the

hidden talent of ferromagnetic nanoparticlesrdquo Chemospherevol 73 no 9 pp 1524ndash1528 2008

[79] J Z Jiang J Zou L H Zhu L Huang H Jiang and YZhang ldquoDegradation of methylene blue with H

2O2activated

by peroxidase-like Fe3O4magnetic nanoparticlesrdquo Journal of

Nanoscience and Nanotechnology vol 11 no 6 pp 4793ndash47992011

[80] L Gao K M Giglio J L Nelson H Sondermann and AJ Travis ldquoFerromagnetic nanoparticles with peroxidase-likeactivity enhance the cleavage of biological macromolecules forbiofilm eliminationrdquo Nanoscale vol 6 no 5 pp 2588ndash25932014

[81] K Vickery A Pajkos and Y Cossart ldquoRemoval of biofilmfrom endoscopes evaluation of detergent efficiencyrdquo AmericanJournal of Infection Control vol 32 no 3 pp 170ndash176 2004

Submit your manuscripts athttpwwwhindawicom

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CorrosionInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Polymer ScienceInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CeramicsJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CompositesJournal of

NanoparticlesJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

Biomaterials

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

NanoscienceJournal of

TextilesHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Journal of

NanotechnologyHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

CrystallographyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CoatingsJournal of

Advances in

Materials Science and EngineeringHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Smart Materials Research

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MetallurgyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

MaterialsJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Nano

materials

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal ofNanomaterials

Page 7: Review Article Recent Research Trends and Future …downloads.hindawi.com/journals/jnm/2015/756278.pdfnovel biosensor, immunoassay, cancer diagnostics, therapeutics, and environmental

Journal of Nanomaterials 7

Table1Va

rious

applicationstu

dies

basedon

nano

zymes

Applicationfield

Nanozym

esAc

tivity

Detectio

nmetho

dDetails

Ref

Biosensor

MNPs

Peroxidase

Colorim

etric

H2O2biosensor

[9]

AuNPs

Glucose

oxidase

Colorim

etric

Nucleicacid

detection

[15]

Carboxyl-m

odified

graphene

oxide

Peroxidase

Colorim

etric

H2O2andglucoseb

iosensor

[23]

MNPs

Peroxidase

Colorim

etric

H2O2andglucoseb

iosensor

[44]

MNPs

Peroxidase

Colorim

etric

H2O2biosensor

[45]

MNPs

Peroxidase

Colorim

etric

H2O2biosensor

[46]

AuNPs

Peroxidase

Colorim

etric

H2O2andglucoseb

iosensor

[47]

MNPs

Peroxidase

Electro

chem

ical

Glucose

biosensor

[48]

MNPs

(with

oxidaseinmesop

orou

scarbo

n)Peroxidase

Electro

chem

ical

Glucose

biosensor

[49]

MNPs

(with

oxidaseinmesop

orou

ssilica)

Peroxidase

Colorim

etric

Glucose

andcholesterolbiosensor

[50]

MNPs

(with

oxidaseinmesop

orou

ssilica)

Peroxidase

Colorim

etric

Galactose

biosensor

[51]

MNPs

(with

oxidaseinmesop

orou

ssilica)

Peroxidase

Colorim

etric

Alcoh

olbiosensor

[52]

MNPs

Peroxidase

Colorim

etric

Nucleicacid

detection(Chlam

ydiatra

chom

atis)

[53]

CeO2NPs

Oxidase

Colorim

etric

Nucleicacid

detection(Chlam

ydiatra

chom

atis)

[56]

Chito

san-mod

ified

MNPs

with

thrombinaptamers

Peroxidase

Colorim

etric

Thrombindetection

[57]

Immun

oassay

MNPs

Peroxidase

Colorim

etric

Cardiactropo

ninI(Tn

I)detection

[9]

MNPs-PtN

Psin

mesop

orou

scarbo

nPeroxidase

Colorim

etric

Rotavirusa

ndHER

2detection

[33]

Graph

eneo

xide

Peroxidase

Colorim

etric

Prostatespecifica

ntigen

(PSA

)detectio

n[41]

Chito

san-mod

ified

MNPs

Peroxidase

Colorim

etric

Mou

seIgGandcarcinoembryonica

ntigen

detection

[63]

Prussia

nblue

mod

ified120574-Fe 2O3NPs

Peroxidase

Colorim

etric

IgGdetection

[64]

Ferritins

Peroxidase

Fluo

rometric

Avidin

andhu

man

ceruloplasmin

detection

[65]

MNPs

Peroxidase

Colorim

etric

Rotavirusa

ndHER

2detection

[66]

MNPs-PtN

Pson

graphene

oxide

Peroxidase

Colorim

etric

fluo

rometric

HER

2detectionandim

aging

[35]

Cancer

diagno

stics

(with

outimmun

ereactio

n)andtherapy

Poly(acrylicacid)-coated

CeO2NPs

Oxidase

Colorim

etric

Lung

cancer

celldetection

[13]

Poly(acrylicacid)-coated

CeO2NPs

Oxidase

Colorim

etric

Lung

andbreastcancer

celldetection

[69]

MagnetoferritinNPs

Peroxidase

Colorim

etric

fluo

rometric

Cancer

cellim

aging

[70]

CeO2NPs

Superoxide

dism

utase

Preventio

nof

retin

aldegeneratio

n[74]

CeO2NPs

Superoxide

dism

utase

Anti-infl

ammation

[75]

Superparam

agnetic

ironoxideN

PsPeroxidase

Prom

otionof

stem

cellgrow

th[76]

Environm

ental

engineering

MNPs

(with

oxidaseinmesop

orou

scarbo

n)Peroxidase

Electro

chem

ical

Phenolcresolandcathecho

ldetectio

n[49]

MNPs

Peroxidase

Colorim

etric

Mela

mined

etectio

n[77]

MNPs

Peroxidase

Removalof

phenol

[78]

MNPs

Peroxidase

Removalof

methylene

blue

[79]

MNPs

Peroxidase

Biofi

lmdegradation

[80]

8 Journal of Nanomaterials

proteins and polysaccharides) as well as killing residentbacteria

4 Conclusions and Future Research Aspects

Nanozymes have recently emerged as a potent alternativeto natural enzymes As discussed above although they arestill in the initial stages of research their use has developedsubstantially inmanydifferent detection and treatmentmeth-ods for biomolecules (Table 1) Despite the advantages ofnanozymes such as their low cost high stability robustnessease of mass production and long-term storability thereare several challenges to be tackled for practical use Firstlymost nanozymes have low activity compared to naturalenzymes Even if the nanomaterial itself is highly activeadditional coating and surface modification can decrease itsperformance Therefore development of novel nanozymesexhibiting high activity and appropriate surface-modificationtechniques are the emerging issues in the field of nanozymesNanozymes also have low selectivity to targets owing to theabsence of active sites where a substrate molecule binds andundergoes a chemical reaction in a natural enzyme Althoughresearchers have designed various types of surface-modifiednanozymes with polymers nucleic acids and antibodiesto provide selectivity mimicking natural enzymes this isstill insufficient for use in practical applications Toxicity ofnanozymes to humans and the ecosystem is also an essentialissue to be solved in regard to environmental and therapeuticapplications

In order for nanozymes to be positioned as a novelsource technology by efficiently overcoming the limitationsof natural enzymes we offer the following suggestions Thedevelopment of new nanozymes with higher activity andother positive properties than existing nanozymes is requiredWhile traditional research on developing nanozymes hasbeen performed by random screening of the enzyme-like activities of existing unspecified nanomaterials futureresearch will follow a strategy of rational screening ofenzyme-like activity based on those atomic compositionswhich are envisaged to catalyze enzymatic reactions Fur-thermore a strategy to prepare composites can be expectedto resolve the current major limitations of nanozymes oflow catalytic activity by exploiting their synergistic effectto facilitate electron transfer between composite materialsduring redox reaction Bioinspired synthesis of nanozymesalso provides an option to prepare nontoxic nanozymesby effectively circumventing the use of toxic chemicals inconventional chemical synthesis thereby accelerating theiruse in therapeutic applications Finally the developmentof novel surface engineering technology that can makenanozymes selective to target substrates will be importantin this field With the abovementioned research projects weexpect nanozymes to be widely employed in a wide range ofapplications in the near future

Conflict of Interests

The authors declare no financial or commercial conflict ofinterests

Acknowledgments

This work was supported by the Basic Science ResearchProgram through theNational Research Foundation of Korea(NRF) funded by the Ministry of Science ICT amp FuturePlanning (NRF-2014R1A1A1006016) and by the Gachon Uni-versity research fund of 2014 (GCU-2014-0110)

References

[1] D L Nelson and M M Cox Lehninger Principles of Biochem-istry vol 6 chapter 6 W H Freeman New York NY USA2005

[2] Z Liu R Cai L Mao H Huang and W Ma ldquoHighly sensitivespectrofluorimetric determination of hydrogen peroxide with120573-cyclodextrin-hemin as catalystrdquo Analyst vol 124 no 2 pp173ndash176 1999

[3] R P Bonar-Law and J K M Sanders ldquoPolyol recognition bya steroid-capped porphyrin Enhancement and modulation ofmisfit guest binding by added water or methanolrdquo Journal of theAmerican Chemical Society vol 117 no 1 pp 259ndash271 1995

[4] X-M Huang M Zhu L-Y Mao and H-X Shen ldquoCat-alytic determination of hydrogen peroxide by using themolybdenum-porphyrin complex as a mimetic enzyme ofperoxidaserdquo Analytical Sciences vol 13 no 1 pp 145ndash147 1997

[5] L Fruk andCMNiemeyer ldquoCovalent hemin-DNAadducts forgenerating a novel class of artificial heme enzymesrdquoAngewandteChemiemdashInternational Edition vol 44 no 17 pp 2603ndash26062005

[6] Q Wang Z Yang X Zhang X Xiao C K Chang and B XuldquoA supramolecular-hydrogel-encapsulated hemin as an artifi-cial enzyme to mimic peroxidaserdquo Angewandte Chemie Inter-national Edition vol 46 no 23 pp 4285ndash4289 2007

[7] Z Genfa and P K Dasgupta ldquoHematin as a peroxidase sub-stitute in hydrogen peroxide determinationsrdquo Analytical Chem-istry vol 64 no 5 pp 517ndash522 1992

[8] H Wei and E Wang ldquoNanomaterials with enzyme-like char-acteristics (nanozymes) next-generation artificial enzymesrdquoChemical Society Reviews vol 42 no 14 pp 6060ndash6093 2013

[9] L Gao J Zhuang LNie et al ldquoIntrinsic peroxidase-like activityof ferromagnetic nanoparticlesrdquo Nature Nanotechnology vol 2no 9 pp 577ndash583 2007

[10] R Polsky R Gill L Kaganovsky and I Willner ldquoNucleic acid-functionalized Pt nanoparticles catalytic labels for the ampli-fied electrochemical detection of biomoleculesrdquo AnalyticalChemistry vol 78 no 7 pp 2268ndash2271 2006

[11] T Li Y Du and E Wang ldquoPolyethyleneimine-functionalizedplatinum nanoparticles with high electrochemiluminescenceactivity and their applications to amplified analysis of bio-moleculesrdquo ChemistrymdashAn Asian Journal vol 3 no 11 pp1942ndash1948 2008

[12] W W He Y Liu J S Yuan et al ldquoAuPt nanostructures asoxidase and peroxidase mimetics for use in immunoassaysrdquoBiomaterials vol 32 no 4 pp 1139ndash1147 2011

[13] A Asati S Santra C Kaittanis S Nath and J M PerezldquoOxidase-like activity of polymer-coated cerium oxide nano-partielesrdquo Angewandte ChemiemdashInternational Edition vol 48no 13 pp 2308ndash2312 2009

[14] W J Luo C F Zhu S Su et al ldquoSelf-catalyzed self-limitinggrowth of glucose oxidase-mimicking gold nanoparticlesrdquo ACSNano vol 4 no 12 pp 7451ndash7458 2010

Journal of Nanomaterials 9

[15] X Zheng Q Liu C Jing et al ldquoCatalytic gold nanoparticles fornanoplasmonic detection of DNA hybridizationrdquo AngewandteChemie International Edition vol 50 no 50 pp 11994ndash119982011

[16] Y J Long Y F Li Y Liu J J Zheng J Tang and C JHuang ldquoVisual observation of the mercury-stimulated peroxi-dase mimetic activity of gold nanoparticlesrdquo Chemical Commu-nications vol 47 no 43 pp 11939ndash11941 2011

[17] W Chen J Chen Y-B Feng et al ldquoPeroxidase-like activityof water-soluble cupric oxide nanoparticles and its analyticalapplication for detection of hydrogen peroxide and glucoserdquoAnalyst vol 137 no 7 pp 1706ndash1712 2012

[18] W Luo Y-S Li J Yuan et al ldquoUltrasensitive fluorometricdetermination of hydrogen peroxide and glucose by usingmultiferroic BiFeO

3nanoparticles as a catalystrdquo Talanta vol 81

no 3 pp 901ndash907 2010[19] S H He W B Shi X D Zhang J A Li and Y M Huang ldquo120573-

Cyclodextrins-based inclusion complexes of CoFe2O4magnetic

nanoparticles as catalyst for the luminol chemiluminescencesystem and their applications in hydrogen peroxide detectionrdquoTalanta vol 82 no 1 pp 377ndash383 2010

[20] W B Shi X D Zhang S H He and Y M Huang ldquoCoFe2O4

magnetic nanoparticles as a peroxidasemimicmediated chemi-luminescence for hydrogen peroxide and glucoserdquo ChemicalCommunications vol 47 no 38 pp 10785ndash10787 2011

[21] Y W Fan and Y M Huang ldquoThe effective peroxidase-likeactivity of chitosan-functionalized CoFe

2O4nanoparticles for

chemiluminescence sensing of hydrogen peroxide and glucoserdquoAnalyst vol 137 no 5 pp 1225ndash1231 2012

[22] A K Dutta S K Maji D N Srivastava et al ldquoSynthesis ofFeS and FeSe nanoparticles from a single source precursor astudy of their photocatalytic activity peroxidase-like behaviorand electrochemical sensing of H

2O2rdquo ACS Applied Materials

and Interfaces vol 4 no 4 pp 1919ndash1927 2012[23] Y Song K Qu C Zhao J Ren and X Qu ldquoGraphene oxide

intrinsic peroxidase catalytic activity and its application toglucose detectionrdquoAdvancedMaterials vol 22 no 19 pp 2206ndash2210 2010

[24] Y Song X Wang C Zhao K Qu J Ren and X Qu ldquoLabel-free colorimetric detection of single nucleotide polymorphismby using single-walled carbon nanotube intrinsic peroxidase-like activityrdquo ChemistrymdashA European Journal vol 16 no 12 pp3617ndash3621 2010

[25] Y Guo J Li and S Dong ldquoHemin functionalized graphenenanosheets-based dual biosensor platforms for hydrogen per-oxide and glucoserdquo Sensors and Actuators B Chemical vol 160no 1 pp 295ndash300 2011

[26] J Xie X Zhang H Wang H Zheng Y Huang and J XieldquoAnalytical and environmental applications of nanoparticles asenzyme mimeticsrdquo TrACmdashTrends in Analytical Chemistry vol39 pp 114ndash129 2012

[27] A K Gupta and M Gupta ldquoSynthesis and surface engineeringof iron oxide nanoparticles for biomedical applicationsrdquoBioma-terials vol 26 no 18 pp 3995ndash4021 2005

[28] J Mu Y Wang M Zhao and L Zhang ldquoIntrinsic peroxidase-like activity and catalase-like activity of Co

3O4nanoparticlesrdquo

Chemical Communications vol 48 no 19 pp 2540ndash2542 2012[29] Y Wan P Qi D Zhang J Wu and Y Wang ldquoMan-

ganese oxide nanowire-mediated enzyme-linked immunosor-bent assayrdquo Biosensors and Bioelectronics vol 33 no 1 pp 69ndash74 2012

[30] R Andre F Natalio M Humanes et al ldquoV2O5nanowires

with an intrinsic peroxidase-like activityrdquo Advanced FunctionalMaterials vol 21 no 3 pp 501ndash509 2011

[31] W Chen J Chen A-L Liu L-M Wang G-W Li and X-H Lin ldquoPeroxidase-like activity of cupric oxide nanoparticlerdquoChemCatChem vol 3 no 7 pp 1151ndash1154 2011

[32] Y-L DongH-G Zhang Z U Rahman et al ldquoGraphene oxide-Fe3O4magnetic nanocomposites with peroxidase-like activity

for colorimetric detection of glucoserdquo Nanoscale vol 4 no 13pp 3969ndash3976 2012

[33] M I Kim Y Ye M-A Woo J Lee and H G Park ldquoA highlyefficient colorimetric immunoassay using a nanocompositeentrapping magnetic and platinum nanoparticles in orderedmesoporous carbonrdquo Advanced Healthcare Materials vol 3 no1 pp 36ndash41 2014

[34] J Liu X Hu S Hou et al ldquoAuPt coreshell nanorods withperoxidase- and ascorbate oxidase-like activities for improveddetection of glucoserdquo Sensors and Actuators B Chemical vol166-167 pp 708ndash714 2012

[35] M I Kim M S Kim M-AWoo et al ldquoHighly efficient colori-metric detection of target cancer cells utilizing superior catalyticactivity of graphene oxide-magnetic-platinum nanohybridsrdquoNanoscale vol 6 no 3 pp 1529ndash1536 2014

[36] M Liu H Zhao S Chen H Yu and X Quan ldquoInterface engi-neering catalytic graphene for smart colorimetric biosensingrdquoACS Nano vol 6 no 4 pp 3142ndash3151 2012

[37] Y Ye T Kong X Yu YWu K Zhang and XWang ldquoEnhancednonenzymatic hydrogen peroxide sensing with reducedgraphene oxideferroferric oxide nanocompositesrdquo Talantavol 89 pp 417ndash421 2012

[38] R Cui Z Han and J-J Zhu ldquoHelical carbon nanotubesintrinsic peroxidase catalytic activity and its application forbiocatalysis and biosensingrdquo ChemistrymdashA European Journalvol 17 no 34 pp 9377ndash9384 2011

[39] M Liu H Zhao S Chen H Yu and X Quan ldquoStimuli-responsive peroxidase mimicking at a smart graphene inter-facerdquo Chemical Communications vol 48 no 56 pp 7055ndash70572012

[40] S Liu J Tian L Wang Y Luo and X Sun ldquoA general strategyfor the production of photoluminescent carbon nitride dotsfrom organic amines and their application as novel peroxidase-like catalysts for colorimetric detection of H

2O2and glucoserdquo

RSC Advances vol 2 no 2 pp 411ndash413 2012[41] F Qu T Li and M Yang ldquoColorimetric platform for visual

detection of cancer biomarker based on intrinsic peroxidaseactivity of graphene oxiderdquo Biosensors and Bioelectronics vol26 no 9 pp 3927ndash3931 2011

[42] W Shi QWang Y Long et al ldquoCarbon nanodots as peroxidasemimetics and their applications to glucose detectionrdquo ChemicalCommunications vol 47 no 23 pp 6695ndash6697 2011

[43] X Wang K Qu B Xu J Ren and X Qu ldquoMulticolorluminescent carbon nanoparticles synthesis supramolecularassembly with porphyrin intrinsic peroxidase-like catalyticactivity and applicationsrdquo Nano Research vol 4 no 9 pp 908ndash920 2011

[44] H Wei and E Wang ldquoFe3O4magnetic nanoparticles as per-

oxidase mimetics and their applications in H2O2and glucose

detectionrdquo Analytical Chemistry vol 80 no 6 pp 2250ndash22542008

[45] Q Chang KDeng L ZhuG Jiang C Yu andH Tang ldquoDeter-mination of hydrogen peroxide with the aid of peroxidase-like

10 Journal of Nanomaterials

Fe3O4magnetic nanoparticles as the catalystrdquo Microchimica

Acta vol 165 no 3-4 pp 299ndash305 2009[46] Z Jiang L Kun H Ouyang A Liang and H Jiang ldquoA simple

and sensitive fluorescence quenching method for the determi-nation of H

2O2using rhodamine B and Fe

3O4nanocatalystrdquo

Journal of Fluorescence vol 21 no 5 pp 2015ndash2020 2011[47] Y Jv B Li andR Cao ldquoPositively-charged gold nanoparticles as

peroxidiase mimic and their application in hydrogen peroxideand glucose detectionrdquo Chemical Communications vol 46 no42 pp 8017ndash8019 2010

[48] K Wang J-J Xu D-C Sun H Wei and X-H Xia ldquoSelectiveglucose detection based on the concept of electrochemicaldepletion of electroactive species in diffusion layerrdquo Biosensorsand Bioelectronics vol 20 no 7 pp 1366ndash1372 2005

[49] M I Kim Y Ye B Y Won S Shin J Lee and H G Park ldquoAhighly efficient electrochemical biosensing platform by employ-ing conductive nanocomposite entrapping magnetic nano-particles and oxidase in mesoporous carbon foamrdquo AdvancedFunctional Materials vol 21 no 15 pp 2868ndash2875 2011

[50] M I Kim J Shim T Li J Lee and H G Park ldquoFabrica-tion of nanoporous nanocomposites entrapping Fe

3O4mag-

netic nanoparticles and oxidases for colorimetric biosensingrdquoChemistrymdashAEuropean Journal vol 17 no 38 pp 10700ndash107072011

[51] M I Kim J Shim T Li et al ldquoColorimetric quantificationof galactose using a nanostructured multi-catalyst systementrapping galactose oxidase and magnetic nanoparticles asperoxidasemimeticsrdquoAnalyst vol 137 no 5 pp 1137ndash1143 2012

[52] M I Kim J Shim H J Parab S C Shin J Lee and H G ParkldquoA convenient alcohol sensor using one-pot nanocompositeentrapping alcohol oxidase and magnetic nanoparticles as per-oxidase mimeticsrdquo Journal of Nanoscience and Nanotechnologyvol 12 no 7 pp 5914ndash5919 2012

[53] K S Park M I Kim D-Y Cho and H G Park ldquoLabel-free colorimetric detection of nucleic acids based on target-induced shielding against the peroxidase-mimicking activity ofmagnetic nanoparticlesrdquo Small vol 7 no 11 pp 1521ndash1525 2011

[54] J A Brinkman M Z Rahmani W E Jones A K Chaturvediand M E Hagensee ldquoOptimization of PCR based detection ofhuman papillomavirus DNA from urine specimensrdquo Journal ofClinical Virology vol 29 no 4 pp 230ndash240 2004

[55] L Hafner K Beagley and P Timms ldquoChlamydia trachomatisinfection host immune responses and potential vaccinesrdquoMucosal Immunology vol 1 no 2 pp 116ndash130 2008

[56] M I Kim K S Park and H G Park ldquoUltrafast colorimetricdetection of nucleic acids based on the inhibition of the oxidaseactivity of cerium oxide nanoparticlesrdquo Chemical Communica-tions vol 50 no 67 pp 9577ndash9580 2014

[57] Z Zhang Z Wang X Wang and X Yang ldquoMagneticnanoparticle-linked colorimetric aptasensor for the detection ofthrombinrdquo Sensors and Actuators B Chemical vol 147 no 2 pp428ndash433 2010

[58] B W Blais and A Martinez-Perez ldquoDetection of groupD salmonellae including Salmonella enteritidis in eggs bypolymyxin-based enzyme-linked immunosorbent assayrdquo Jour-nal of Food Protection vol 71 no 2 pp 392ndash396 2008

[59] V Tripathi S Nara S K Chaube et al ldquoDevelopment ofrapid and sensitive one-step direct enzyme linked immunosor-bent assay for 17-120572-OH-progesterone in serumrdquo Journal ofImmunoassay and Immunochemistry vol 29 no 2 pp 117ndash1272008

[60] K DMcReynolds M J Hadd and J Gervay-Hague ldquoSynthesisof biotinylated glycoconjugates and their use in a novel ELISAfor direct comparison ofHIV-1 gp120 recognition ofGalCer andrelated carbohydrate analoguesrdquo Bioconjugate Chemistry vol10 no 6 pp 1021ndash1031 1999

[61] H Hocini S Iscaki J-P Bouvet M D Kazatchkine and LBelec ldquoAn ELISA method to measure total and specific humansecretory IgA subclasses based on selective degradation by IgA1-proteaserdquo Journal of Immunological Methods vol 235 no 1-2pp 53ndash60 2000

[62] L Micheli S Di Stefano D Moscone et al ldquoProduction ofantibodies and development of highly sensitive formats ofenzyme immunoassay for saxitoxin analysisrdquo Analytical andBioanalytical Chemistry vol 373 no 8 pp 678ndash684 2002

[63] L Gao J Wu S Lyle K Zehr L Cao and D Gao ldquoMagnetitenanoparticle-linked immunosorbent assayrdquo Journal of PhysicalChemistry C vol 112 no 44 pp 17357ndash17361 2008

[64] X-Q Zhang S-W Gong Y Zhang T Yang C-YWang andNGu ldquoPrussian blue modified iron oxide magnetic nanoparticlesand their high peroxidase-like activityrdquo Journal of MaterialsChemistry vol 20 no 24 pp 5110ndash5116 2010

[65] Z Tang H Wu Y Zhang Z Li and Y Lin ldquoEnzyme-mimicactivity of ferric nano-core residing in ferritin and its biosensingapplicationsrdquo Analytical Chemistry vol 83 no 22 pp 8611ndash8616 2011

[66] M-A Woo M I Kim J H Jung K S Park T S Seoand H G Park ldquoA novel colorimetric immunoassay utilizingthe peroxidase mimicking activity of magnetic nanoparticlesrdquoInternational Journal of Molecular Sciences vol 14 no 5 pp9999ndash10014 2013

[67] V H C Bramwell G S Doig A B Tuck et al ldquoChangesover time of extracellular domain of HER2 (ECDHER2) serumlevels have prognostic value in metastatic breast cancerrdquo BreastCancer Research andTreatment vol 114 no 3 pp 503ndash511 2009

[68] K S Asgeirsson A Agrawal C Allen et al ldquoSerum epidermalgrowth factor receptor and HER2 expression in primary andmetastatic breast cancer patientsrdquo Breast Cancer Research vol9 no 6 article R75 2007

[69] A Asati C Kaittanis S Santra and J M Perez ldquoPH-tunableoxidase-like activity of cerium oxide nanoparticles achievingsensitive fluorigenic detection of cancer biomarkers at neutralpHrdquo Analytical Chemistry vol 83 no 7 pp 2547ndash2553 2011

[70] K L Fan C Q Cao Y X Pan et al ldquoMagnetoferritinnanoparticles for targeting and visualizing tumour tissuesrdquoNature Nanotechnology vol 7 no 7 pp 459ndash464 2012

[71] S Beatty H-H Koh M Phil D Henson and M BoultonldquoThe role of oxidative stress in the pathogenesis of age-relatedmacular degenerationrdquo Survey of Ophthalmology vol 45 no 2pp 115ndash134 2000

[72] C Korsvik S Patil S Seal and W T Self ldquoSuperoxidedismutase mimetic properties exhibited by vacancy engineeredceria nanoparticlesrdquo Chemical Communications no 10 pp1056ndash1058 2007

[73] E G Heckert A S Karakoti S Seal andW T Self ldquoThe role ofcerium redox state in the SOD mimetic activity of nanoceriardquoBiomaterials vol 29 no 18 pp 2705ndash2709 2008

[74] J Chen S Patil S Seal and J F McGinnis ldquoRare earthnanoparticles prevent retinal degeneration induced by intracel-lular peroxidesrdquo Nature Nanotechnology vol 1 no 2 pp 142ndash150 2006

Journal of Nanomaterials 11

[75] S M Hirst A S Karakoti R D Tyler N Sriranganathan SSeal and C M Reilly ldquoAnti-inflammatory properties of ceriumoxide nanoparticlesrdquo Small vol 5 no 24 pp 2848ndash2856 2009

[76] D-M Huang J-K Hsiao Y-C Chen et al ldquoThe promotion ofhuman mesenchymal stem cell proliferation by superparamag-netic iron oxide nanoparticlesrdquo Biomaterials vol 30 no 22 pp3645ndash3651 2009

[77] N Ding N Yan C Ren and X Chen ldquoColorimetric determi-nation of melamine in dairy products by Fe

3O4Magnetic nano-

particles-H2O2-ABTS detection systemrdquo Analytical Chemistry

vol 82 no 13 pp 5897ndash5899 2010[78] J Zhang J Zhuang L Gao et al ldquoDecomposing phenol by the

hidden talent of ferromagnetic nanoparticlesrdquo Chemospherevol 73 no 9 pp 1524ndash1528 2008

[79] J Z Jiang J Zou L H Zhu L Huang H Jiang and YZhang ldquoDegradation of methylene blue with H

2O2activated

by peroxidase-like Fe3O4magnetic nanoparticlesrdquo Journal of

Nanoscience and Nanotechnology vol 11 no 6 pp 4793ndash47992011

[80] L Gao K M Giglio J L Nelson H Sondermann and AJ Travis ldquoFerromagnetic nanoparticles with peroxidase-likeactivity enhance the cleavage of biological macromolecules forbiofilm eliminationrdquo Nanoscale vol 6 no 5 pp 2588ndash25932014

[81] K Vickery A Pajkos and Y Cossart ldquoRemoval of biofilmfrom endoscopes evaluation of detergent efficiencyrdquo AmericanJournal of Infection Control vol 32 no 3 pp 170ndash176 2004

Submit your manuscripts athttpwwwhindawicom

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CorrosionInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Polymer ScienceInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CeramicsJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CompositesJournal of

NanoparticlesJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

Biomaterials

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

NanoscienceJournal of

TextilesHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Journal of

NanotechnologyHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

CrystallographyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CoatingsJournal of

Advances in

Materials Science and EngineeringHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Smart Materials Research

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MetallurgyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

MaterialsJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Nano

materials

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal ofNanomaterials

Page 8: Review Article Recent Research Trends and Future …downloads.hindawi.com/journals/jnm/2015/756278.pdfnovel biosensor, immunoassay, cancer diagnostics, therapeutics, and environmental

8 Journal of Nanomaterials

proteins and polysaccharides) as well as killing residentbacteria

4 Conclusions and Future Research Aspects

Nanozymes have recently emerged as a potent alternativeto natural enzymes As discussed above although they arestill in the initial stages of research their use has developedsubstantially inmanydifferent detection and treatmentmeth-ods for biomolecules (Table 1) Despite the advantages ofnanozymes such as their low cost high stability robustnessease of mass production and long-term storability thereare several challenges to be tackled for practical use Firstlymost nanozymes have low activity compared to naturalenzymes Even if the nanomaterial itself is highly activeadditional coating and surface modification can decrease itsperformance Therefore development of novel nanozymesexhibiting high activity and appropriate surface-modificationtechniques are the emerging issues in the field of nanozymesNanozymes also have low selectivity to targets owing to theabsence of active sites where a substrate molecule binds andundergoes a chemical reaction in a natural enzyme Althoughresearchers have designed various types of surface-modifiednanozymes with polymers nucleic acids and antibodiesto provide selectivity mimicking natural enzymes this isstill insufficient for use in practical applications Toxicity ofnanozymes to humans and the ecosystem is also an essentialissue to be solved in regard to environmental and therapeuticapplications

In order for nanozymes to be positioned as a novelsource technology by efficiently overcoming the limitationsof natural enzymes we offer the following suggestions Thedevelopment of new nanozymes with higher activity andother positive properties than existing nanozymes is requiredWhile traditional research on developing nanozymes hasbeen performed by random screening of the enzyme-like activities of existing unspecified nanomaterials futureresearch will follow a strategy of rational screening ofenzyme-like activity based on those atomic compositionswhich are envisaged to catalyze enzymatic reactions Fur-thermore a strategy to prepare composites can be expectedto resolve the current major limitations of nanozymes oflow catalytic activity by exploiting their synergistic effectto facilitate electron transfer between composite materialsduring redox reaction Bioinspired synthesis of nanozymesalso provides an option to prepare nontoxic nanozymesby effectively circumventing the use of toxic chemicals inconventional chemical synthesis thereby accelerating theiruse in therapeutic applications Finally the developmentof novel surface engineering technology that can makenanozymes selective to target substrates will be importantin this field With the abovementioned research projects weexpect nanozymes to be widely employed in a wide range ofapplications in the near future

Conflict of Interests

The authors declare no financial or commercial conflict ofinterests

Acknowledgments

This work was supported by the Basic Science ResearchProgram through theNational Research Foundation of Korea(NRF) funded by the Ministry of Science ICT amp FuturePlanning (NRF-2014R1A1A1006016) and by the Gachon Uni-versity research fund of 2014 (GCU-2014-0110)

References

[1] D L Nelson and M M Cox Lehninger Principles of Biochem-istry vol 6 chapter 6 W H Freeman New York NY USA2005

[2] Z Liu R Cai L Mao H Huang and W Ma ldquoHighly sensitivespectrofluorimetric determination of hydrogen peroxide with120573-cyclodextrin-hemin as catalystrdquo Analyst vol 124 no 2 pp173ndash176 1999

[3] R P Bonar-Law and J K M Sanders ldquoPolyol recognition bya steroid-capped porphyrin Enhancement and modulation ofmisfit guest binding by added water or methanolrdquo Journal of theAmerican Chemical Society vol 117 no 1 pp 259ndash271 1995

[4] X-M Huang M Zhu L-Y Mao and H-X Shen ldquoCat-alytic determination of hydrogen peroxide by using themolybdenum-porphyrin complex as a mimetic enzyme ofperoxidaserdquo Analytical Sciences vol 13 no 1 pp 145ndash147 1997

[5] L Fruk andCMNiemeyer ldquoCovalent hemin-DNAadducts forgenerating a novel class of artificial heme enzymesrdquoAngewandteChemiemdashInternational Edition vol 44 no 17 pp 2603ndash26062005

[6] Q Wang Z Yang X Zhang X Xiao C K Chang and B XuldquoA supramolecular-hydrogel-encapsulated hemin as an artifi-cial enzyme to mimic peroxidaserdquo Angewandte Chemie Inter-national Edition vol 46 no 23 pp 4285ndash4289 2007

[7] Z Genfa and P K Dasgupta ldquoHematin as a peroxidase sub-stitute in hydrogen peroxide determinationsrdquo Analytical Chem-istry vol 64 no 5 pp 517ndash522 1992

[8] H Wei and E Wang ldquoNanomaterials with enzyme-like char-acteristics (nanozymes) next-generation artificial enzymesrdquoChemical Society Reviews vol 42 no 14 pp 6060ndash6093 2013

[9] L Gao J Zhuang LNie et al ldquoIntrinsic peroxidase-like activityof ferromagnetic nanoparticlesrdquo Nature Nanotechnology vol 2no 9 pp 577ndash583 2007

[10] R Polsky R Gill L Kaganovsky and I Willner ldquoNucleic acid-functionalized Pt nanoparticles catalytic labels for the ampli-fied electrochemical detection of biomoleculesrdquo AnalyticalChemistry vol 78 no 7 pp 2268ndash2271 2006

[11] T Li Y Du and E Wang ldquoPolyethyleneimine-functionalizedplatinum nanoparticles with high electrochemiluminescenceactivity and their applications to amplified analysis of bio-moleculesrdquo ChemistrymdashAn Asian Journal vol 3 no 11 pp1942ndash1948 2008

[12] W W He Y Liu J S Yuan et al ldquoAuPt nanostructures asoxidase and peroxidase mimetics for use in immunoassaysrdquoBiomaterials vol 32 no 4 pp 1139ndash1147 2011

[13] A Asati S Santra C Kaittanis S Nath and J M PerezldquoOxidase-like activity of polymer-coated cerium oxide nano-partielesrdquo Angewandte ChemiemdashInternational Edition vol 48no 13 pp 2308ndash2312 2009

[14] W J Luo C F Zhu S Su et al ldquoSelf-catalyzed self-limitinggrowth of glucose oxidase-mimicking gold nanoparticlesrdquo ACSNano vol 4 no 12 pp 7451ndash7458 2010

Journal of Nanomaterials 9

[15] X Zheng Q Liu C Jing et al ldquoCatalytic gold nanoparticles fornanoplasmonic detection of DNA hybridizationrdquo AngewandteChemie International Edition vol 50 no 50 pp 11994ndash119982011

[16] Y J Long Y F Li Y Liu J J Zheng J Tang and C JHuang ldquoVisual observation of the mercury-stimulated peroxi-dase mimetic activity of gold nanoparticlesrdquo Chemical Commu-nications vol 47 no 43 pp 11939ndash11941 2011

[17] W Chen J Chen Y-B Feng et al ldquoPeroxidase-like activityof water-soluble cupric oxide nanoparticles and its analyticalapplication for detection of hydrogen peroxide and glucoserdquoAnalyst vol 137 no 7 pp 1706ndash1712 2012

[18] W Luo Y-S Li J Yuan et al ldquoUltrasensitive fluorometricdetermination of hydrogen peroxide and glucose by usingmultiferroic BiFeO

3nanoparticles as a catalystrdquo Talanta vol 81

no 3 pp 901ndash907 2010[19] S H He W B Shi X D Zhang J A Li and Y M Huang ldquo120573-

Cyclodextrins-based inclusion complexes of CoFe2O4magnetic

nanoparticles as catalyst for the luminol chemiluminescencesystem and their applications in hydrogen peroxide detectionrdquoTalanta vol 82 no 1 pp 377ndash383 2010

[20] W B Shi X D Zhang S H He and Y M Huang ldquoCoFe2O4

magnetic nanoparticles as a peroxidasemimicmediated chemi-luminescence for hydrogen peroxide and glucoserdquo ChemicalCommunications vol 47 no 38 pp 10785ndash10787 2011

[21] Y W Fan and Y M Huang ldquoThe effective peroxidase-likeactivity of chitosan-functionalized CoFe

2O4nanoparticles for

chemiluminescence sensing of hydrogen peroxide and glucoserdquoAnalyst vol 137 no 5 pp 1225ndash1231 2012

[22] A K Dutta S K Maji D N Srivastava et al ldquoSynthesis ofFeS and FeSe nanoparticles from a single source precursor astudy of their photocatalytic activity peroxidase-like behaviorand electrochemical sensing of H

2O2rdquo ACS Applied Materials

and Interfaces vol 4 no 4 pp 1919ndash1927 2012[23] Y Song K Qu C Zhao J Ren and X Qu ldquoGraphene oxide

intrinsic peroxidase catalytic activity and its application toglucose detectionrdquoAdvancedMaterials vol 22 no 19 pp 2206ndash2210 2010

[24] Y Song X Wang C Zhao K Qu J Ren and X Qu ldquoLabel-free colorimetric detection of single nucleotide polymorphismby using single-walled carbon nanotube intrinsic peroxidase-like activityrdquo ChemistrymdashA European Journal vol 16 no 12 pp3617ndash3621 2010

[25] Y Guo J Li and S Dong ldquoHemin functionalized graphenenanosheets-based dual biosensor platforms for hydrogen per-oxide and glucoserdquo Sensors and Actuators B Chemical vol 160no 1 pp 295ndash300 2011

[26] J Xie X Zhang H Wang H Zheng Y Huang and J XieldquoAnalytical and environmental applications of nanoparticles asenzyme mimeticsrdquo TrACmdashTrends in Analytical Chemistry vol39 pp 114ndash129 2012

[27] A K Gupta and M Gupta ldquoSynthesis and surface engineeringof iron oxide nanoparticles for biomedical applicationsrdquoBioma-terials vol 26 no 18 pp 3995ndash4021 2005

[28] J Mu Y Wang M Zhao and L Zhang ldquoIntrinsic peroxidase-like activity and catalase-like activity of Co

3O4nanoparticlesrdquo

Chemical Communications vol 48 no 19 pp 2540ndash2542 2012[29] Y Wan P Qi D Zhang J Wu and Y Wang ldquoMan-

ganese oxide nanowire-mediated enzyme-linked immunosor-bent assayrdquo Biosensors and Bioelectronics vol 33 no 1 pp 69ndash74 2012

[30] R Andre F Natalio M Humanes et al ldquoV2O5nanowires

with an intrinsic peroxidase-like activityrdquo Advanced FunctionalMaterials vol 21 no 3 pp 501ndash509 2011

[31] W Chen J Chen A-L Liu L-M Wang G-W Li and X-H Lin ldquoPeroxidase-like activity of cupric oxide nanoparticlerdquoChemCatChem vol 3 no 7 pp 1151ndash1154 2011

[32] Y-L DongH-G Zhang Z U Rahman et al ldquoGraphene oxide-Fe3O4magnetic nanocomposites with peroxidase-like activity

for colorimetric detection of glucoserdquo Nanoscale vol 4 no 13pp 3969ndash3976 2012

[33] M I Kim Y Ye M-A Woo J Lee and H G Park ldquoA highlyefficient colorimetric immunoassay using a nanocompositeentrapping magnetic and platinum nanoparticles in orderedmesoporous carbonrdquo Advanced Healthcare Materials vol 3 no1 pp 36ndash41 2014

[34] J Liu X Hu S Hou et al ldquoAuPt coreshell nanorods withperoxidase- and ascorbate oxidase-like activities for improveddetection of glucoserdquo Sensors and Actuators B Chemical vol166-167 pp 708ndash714 2012

[35] M I Kim M S Kim M-AWoo et al ldquoHighly efficient colori-metric detection of target cancer cells utilizing superior catalyticactivity of graphene oxide-magnetic-platinum nanohybridsrdquoNanoscale vol 6 no 3 pp 1529ndash1536 2014

[36] M Liu H Zhao S Chen H Yu and X Quan ldquoInterface engi-neering catalytic graphene for smart colorimetric biosensingrdquoACS Nano vol 6 no 4 pp 3142ndash3151 2012

[37] Y Ye T Kong X Yu YWu K Zhang and XWang ldquoEnhancednonenzymatic hydrogen peroxide sensing with reducedgraphene oxideferroferric oxide nanocompositesrdquo Talantavol 89 pp 417ndash421 2012

[38] R Cui Z Han and J-J Zhu ldquoHelical carbon nanotubesintrinsic peroxidase catalytic activity and its application forbiocatalysis and biosensingrdquo ChemistrymdashA European Journalvol 17 no 34 pp 9377ndash9384 2011

[39] M Liu H Zhao S Chen H Yu and X Quan ldquoStimuli-responsive peroxidase mimicking at a smart graphene inter-facerdquo Chemical Communications vol 48 no 56 pp 7055ndash70572012

[40] S Liu J Tian L Wang Y Luo and X Sun ldquoA general strategyfor the production of photoluminescent carbon nitride dotsfrom organic amines and their application as novel peroxidase-like catalysts for colorimetric detection of H

2O2and glucoserdquo

RSC Advances vol 2 no 2 pp 411ndash413 2012[41] F Qu T Li and M Yang ldquoColorimetric platform for visual

detection of cancer biomarker based on intrinsic peroxidaseactivity of graphene oxiderdquo Biosensors and Bioelectronics vol26 no 9 pp 3927ndash3931 2011

[42] W Shi QWang Y Long et al ldquoCarbon nanodots as peroxidasemimetics and their applications to glucose detectionrdquo ChemicalCommunications vol 47 no 23 pp 6695ndash6697 2011

[43] X Wang K Qu B Xu J Ren and X Qu ldquoMulticolorluminescent carbon nanoparticles synthesis supramolecularassembly with porphyrin intrinsic peroxidase-like catalyticactivity and applicationsrdquo Nano Research vol 4 no 9 pp 908ndash920 2011

[44] H Wei and E Wang ldquoFe3O4magnetic nanoparticles as per-

oxidase mimetics and their applications in H2O2and glucose

detectionrdquo Analytical Chemistry vol 80 no 6 pp 2250ndash22542008

[45] Q Chang KDeng L ZhuG Jiang C Yu andH Tang ldquoDeter-mination of hydrogen peroxide with the aid of peroxidase-like

10 Journal of Nanomaterials

Fe3O4magnetic nanoparticles as the catalystrdquo Microchimica

Acta vol 165 no 3-4 pp 299ndash305 2009[46] Z Jiang L Kun H Ouyang A Liang and H Jiang ldquoA simple

and sensitive fluorescence quenching method for the determi-nation of H

2O2using rhodamine B and Fe

3O4nanocatalystrdquo

Journal of Fluorescence vol 21 no 5 pp 2015ndash2020 2011[47] Y Jv B Li andR Cao ldquoPositively-charged gold nanoparticles as

peroxidiase mimic and their application in hydrogen peroxideand glucose detectionrdquo Chemical Communications vol 46 no42 pp 8017ndash8019 2010

[48] K Wang J-J Xu D-C Sun H Wei and X-H Xia ldquoSelectiveglucose detection based on the concept of electrochemicaldepletion of electroactive species in diffusion layerrdquo Biosensorsand Bioelectronics vol 20 no 7 pp 1366ndash1372 2005

[49] M I Kim Y Ye B Y Won S Shin J Lee and H G Park ldquoAhighly efficient electrochemical biosensing platform by employ-ing conductive nanocomposite entrapping magnetic nano-particles and oxidase in mesoporous carbon foamrdquo AdvancedFunctional Materials vol 21 no 15 pp 2868ndash2875 2011

[50] M I Kim J Shim T Li J Lee and H G Park ldquoFabrica-tion of nanoporous nanocomposites entrapping Fe

3O4mag-

netic nanoparticles and oxidases for colorimetric biosensingrdquoChemistrymdashAEuropean Journal vol 17 no 38 pp 10700ndash107072011

[51] M I Kim J Shim T Li et al ldquoColorimetric quantificationof galactose using a nanostructured multi-catalyst systementrapping galactose oxidase and magnetic nanoparticles asperoxidasemimeticsrdquoAnalyst vol 137 no 5 pp 1137ndash1143 2012

[52] M I Kim J Shim H J Parab S C Shin J Lee and H G ParkldquoA convenient alcohol sensor using one-pot nanocompositeentrapping alcohol oxidase and magnetic nanoparticles as per-oxidase mimeticsrdquo Journal of Nanoscience and Nanotechnologyvol 12 no 7 pp 5914ndash5919 2012

[53] K S Park M I Kim D-Y Cho and H G Park ldquoLabel-free colorimetric detection of nucleic acids based on target-induced shielding against the peroxidase-mimicking activity ofmagnetic nanoparticlesrdquo Small vol 7 no 11 pp 1521ndash1525 2011

[54] J A Brinkman M Z Rahmani W E Jones A K Chaturvediand M E Hagensee ldquoOptimization of PCR based detection ofhuman papillomavirus DNA from urine specimensrdquo Journal ofClinical Virology vol 29 no 4 pp 230ndash240 2004

[55] L Hafner K Beagley and P Timms ldquoChlamydia trachomatisinfection host immune responses and potential vaccinesrdquoMucosal Immunology vol 1 no 2 pp 116ndash130 2008

[56] M I Kim K S Park and H G Park ldquoUltrafast colorimetricdetection of nucleic acids based on the inhibition of the oxidaseactivity of cerium oxide nanoparticlesrdquo Chemical Communica-tions vol 50 no 67 pp 9577ndash9580 2014

[57] Z Zhang Z Wang X Wang and X Yang ldquoMagneticnanoparticle-linked colorimetric aptasensor for the detection ofthrombinrdquo Sensors and Actuators B Chemical vol 147 no 2 pp428ndash433 2010

[58] B W Blais and A Martinez-Perez ldquoDetection of groupD salmonellae including Salmonella enteritidis in eggs bypolymyxin-based enzyme-linked immunosorbent assayrdquo Jour-nal of Food Protection vol 71 no 2 pp 392ndash396 2008

[59] V Tripathi S Nara S K Chaube et al ldquoDevelopment ofrapid and sensitive one-step direct enzyme linked immunosor-bent assay for 17-120572-OH-progesterone in serumrdquo Journal ofImmunoassay and Immunochemistry vol 29 no 2 pp 117ndash1272008

[60] K DMcReynolds M J Hadd and J Gervay-Hague ldquoSynthesisof biotinylated glycoconjugates and their use in a novel ELISAfor direct comparison ofHIV-1 gp120 recognition ofGalCer andrelated carbohydrate analoguesrdquo Bioconjugate Chemistry vol10 no 6 pp 1021ndash1031 1999

[61] H Hocini S Iscaki J-P Bouvet M D Kazatchkine and LBelec ldquoAn ELISA method to measure total and specific humansecretory IgA subclasses based on selective degradation by IgA1-proteaserdquo Journal of Immunological Methods vol 235 no 1-2pp 53ndash60 2000

[62] L Micheli S Di Stefano D Moscone et al ldquoProduction ofantibodies and development of highly sensitive formats ofenzyme immunoassay for saxitoxin analysisrdquo Analytical andBioanalytical Chemistry vol 373 no 8 pp 678ndash684 2002

[63] L Gao J Wu S Lyle K Zehr L Cao and D Gao ldquoMagnetitenanoparticle-linked immunosorbent assayrdquo Journal of PhysicalChemistry C vol 112 no 44 pp 17357ndash17361 2008

[64] X-Q Zhang S-W Gong Y Zhang T Yang C-YWang andNGu ldquoPrussian blue modified iron oxide magnetic nanoparticlesand their high peroxidase-like activityrdquo Journal of MaterialsChemistry vol 20 no 24 pp 5110ndash5116 2010

[65] Z Tang H Wu Y Zhang Z Li and Y Lin ldquoEnzyme-mimicactivity of ferric nano-core residing in ferritin and its biosensingapplicationsrdquo Analytical Chemistry vol 83 no 22 pp 8611ndash8616 2011

[66] M-A Woo M I Kim J H Jung K S Park T S Seoand H G Park ldquoA novel colorimetric immunoassay utilizingthe peroxidase mimicking activity of magnetic nanoparticlesrdquoInternational Journal of Molecular Sciences vol 14 no 5 pp9999ndash10014 2013

[67] V H C Bramwell G S Doig A B Tuck et al ldquoChangesover time of extracellular domain of HER2 (ECDHER2) serumlevels have prognostic value in metastatic breast cancerrdquo BreastCancer Research andTreatment vol 114 no 3 pp 503ndash511 2009

[68] K S Asgeirsson A Agrawal C Allen et al ldquoSerum epidermalgrowth factor receptor and HER2 expression in primary andmetastatic breast cancer patientsrdquo Breast Cancer Research vol9 no 6 article R75 2007

[69] A Asati C Kaittanis S Santra and J M Perez ldquoPH-tunableoxidase-like activity of cerium oxide nanoparticles achievingsensitive fluorigenic detection of cancer biomarkers at neutralpHrdquo Analytical Chemistry vol 83 no 7 pp 2547ndash2553 2011

[70] K L Fan C Q Cao Y X Pan et al ldquoMagnetoferritinnanoparticles for targeting and visualizing tumour tissuesrdquoNature Nanotechnology vol 7 no 7 pp 459ndash464 2012

[71] S Beatty H-H Koh M Phil D Henson and M BoultonldquoThe role of oxidative stress in the pathogenesis of age-relatedmacular degenerationrdquo Survey of Ophthalmology vol 45 no 2pp 115ndash134 2000

[72] C Korsvik S Patil S Seal and W T Self ldquoSuperoxidedismutase mimetic properties exhibited by vacancy engineeredceria nanoparticlesrdquo Chemical Communications no 10 pp1056ndash1058 2007

[73] E G Heckert A S Karakoti S Seal andW T Self ldquoThe role ofcerium redox state in the SOD mimetic activity of nanoceriardquoBiomaterials vol 29 no 18 pp 2705ndash2709 2008

[74] J Chen S Patil S Seal and J F McGinnis ldquoRare earthnanoparticles prevent retinal degeneration induced by intracel-lular peroxidesrdquo Nature Nanotechnology vol 1 no 2 pp 142ndash150 2006

Journal of Nanomaterials 11

[75] S M Hirst A S Karakoti R D Tyler N Sriranganathan SSeal and C M Reilly ldquoAnti-inflammatory properties of ceriumoxide nanoparticlesrdquo Small vol 5 no 24 pp 2848ndash2856 2009

[76] D-M Huang J-K Hsiao Y-C Chen et al ldquoThe promotion ofhuman mesenchymal stem cell proliferation by superparamag-netic iron oxide nanoparticlesrdquo Biomaterials vol 30 no 22 pp3645ndash3651 2009

[77] N Ding N Yan C Ren and X Chen ldquoColorimetric determi-nation of melamine in dairy products by Fe

3O4Magnetic nano-

particles-H2O2-ABTS detection systemrdquo Analytical Chemistry

vol 82 no 13 pp 5897ndash5899 2010[78] J Zhang J Zhuang L Gao et al ldquoDecomposing phenol by the

hidden talent of ferromagnetic nanoparticlesrdquo Chemospherevol 73 no 9 pp 1524ndash1528 2008

[79] J Z Jiang J Zou L H Zhu L Huang H Jiang and YZhang ldquoDegradation of methylene blue with H

2O2activated

by peroxidase-like Fe3O4magnetic nanoparticlesrdquo Journal of

Nanoscience and Nanotechnology vol 11 no 6 pp 4793ndash47992011

[80] L Gao K M Giglio J L Nelson H Sondermann and AJ Travis ldquoFerromagnetic nanoparticles with peroxidase-likeactivity enhance the cleavage of biological macromolecules forbiofilm eliminationrdquo Nanoscale vol 6 no 5 pp 2588ndash25932014

[81] K Vickery A Pajkos and Y Cossart ldquoRemoval of biofilmfrom endoscopes evaluation of detergent efficiencyrdquo AmericanJournal of Infection Control vol 32 no 3 pp 170ndash176 2004

Submit your manuscripts athttpwwwhindawicom

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CorrosionInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Polymer ScienceInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CeramicsJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CompositesJournal of

NanoparticlesJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

Biomaterials

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

NanoscienceJournal of

TextilesHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Journal of

NanotechnologyHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

CrystallographyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CoatingsJournal of

Advances in

Materials Science and EngineeringHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Smart Materials Research

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MetallurgyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

MaterialsJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Nano

materials

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal ofNanomaterials

Page 9: Review Article Recent Research Trends and Future …downloads.hindawi.com/journals/jnm/2015/756278.pdfnovel biosensor, immunoassay, cancer diagnostics, therapeutics, and environmental

Journal of Nanomaterials 9

[15] X Zheng Q Liu C Jing et al ldquoCatalytic gold nanoparticles fornanoplasmonic detection of DNA hybridizationrdquo AngewandteChemie International Edition vol 50 no 50 pp 11994ndash119982011

[16] Y J Long Y F Li Y Liu J J Zheng J Tang and C JHuang ldquoVisual observation of the mercury-stimulated peroxi-dase mimetic activity of gold nanoparticlesrdquo Chemical Commu-nications vol 47 no 43 pp 11939ndash11941 2011

[17] W Chen J Chen Y-B Feng et al ldquoPeroxidase-like activityof water-soluble cupric oxide nanoparticles and its analyticalapplication for detection of hydrogen peroxide and glucoserdquoAnalyst vol 137 no 7 pp 1706ndash1712 2012

[18] W Luo Y-S Li J Yuan et al ldquoUltrasensitive fluorometricdetermination of hydrogen peroxide and glucose by usingmultiferroic BiFeO

3nanoparticles as a catalystrdquo Talanta vol 81

no 3 pp 901ndash907 2010[19] S H He W B Shi X D Zhang J A Li and Y M Huang ldquo120573-

Cyclodextrins-based inclusion complexes of CoFe2O4magnetic

nanoparticles as catalyst for the luminol chemiluminescencesystem and their applications in hydrogen peroxide detectionrdquoTalanta vol 82 no 1 pp 377ndash383 2010

[20] W B Shi X D Zhang S H He and Y M Huang ldquoCoFe2O4

magnetic nanoparticles as a peroxidasemimicmediated chemi-luminescence for hydrogen peroxide and glucoserdquo ChemicalCommunications vol 47 no 38 pp 10785ndash10787 2011

[21] Y W Fan and Y M Huang ldquoThe effective peroxidase-likeactivity of chitosan-functionalized CoFe

2O4nanoparticles for

chemiluminescence sensing of hydrogen peroxide and glucoserdquoAnalyst vol 137 no 5 pp 1225ndash1231 2012

[22] A K Dutta S K Maji D N Srivastava et al ldquoSynthesis ofFeS and FeSe nanoparticles from a single source precursor astudy of their photocatalytic activity peroxidase-like behaviorand electrochemical sensing of H

2O2rdquo ACS Applied Materials

and Interfaces vol 4 no 4 pp 1919ndash1927 2012[23] Y Song K Qu C Zhao J Ren and X Qu ldquoGraphene oxide

intrinsic peroxidase catalytic activity and its application toglucose detectionrdquoAdvancedMaterials vol 22 no 19 pp 2206ndash2210 2010

[24] Y Song X Wang C Zhao K Qu J Ren and X Qu ldquoLabel-free colorimetric detection of single nucleotide polymorphismby using single-walled carbon nanotube intrinsic peroxidase-like activityrdquo ChemistrymdashA European Journal vol 16 no 12 pp3617ndash3621 2010

[25] Y Guo J Li and S Dong ldquoHemin functionalized graphenenanosheets-based dual biosensor platforms for hydrogen per-oxide and glucoserdquo Sensors and Actuators B Chemical vol 160no 1 pp 295ndash300 2011

[26] J Xie X Zhang H Wang H Zheng Y Huang and J XieldquoAnalytical and environmental applications of nanoparticles asenzyme mimeticsrdquo TrACmdashTrends in Analytical Chemistry vol39 pp 114ndash129 2012

[27] A K Gupta and M Gupta ldquoSynthesis and surface engineeringof iron oxide nanoparticles for biomedical applicationsrdquoBioma-terials vol 26 no 18 pp 3995ndash4021 2005

[28] J Mu Y Wang M Zhao and L Zhang ldquoIntrinsic peroxidase-like activity and catalase-like activity of Co

3O4nanoparticlesrdquo

Chemical Communications vol 48 no 19 pp 2540ndash2542 2012[29] Y Wan P Qi D Zhang J Wu and Y Wang ldquoMan-

ganese oxide nanowire-mediated enzyme-linked immunosor-bent assayrdquo Biosensors and Bioelectronics vol 33 no 1 pp 69ndash74 2012

[30] R Andre F Natalio M Humanes et al ldquoV2O5nanowires

with an intrinsic peroxidase-like activityrdquo Advanced FunctionalMaterials vol 21 no 3 pp 501ndash509 2011

[31] W Chen J Chen A-L Liu L-M Wang G-W Li and X-H Lin ldquoPeroxidase-like activity of cupric oxide nanoparticlerdquoChemCatChem vol 3 no 7 pp 1151ndash1154 2011

[32] Y-L DongH-G Zhang Z U Rahman et al ldquoGraphene oxide-Fe3O4magnetic nanocomposites with peroxidase-like activity

for colorimetric detection of glucoserdquo Nanoscale vol 4 no 13pp 3969ndash3976 2012

[33] M I Kim Y Ye M-A Woo J Lee and H G Park ldquoA highlyefficient colorimetric immunoassay using a nanocompositeentrapping magnetic and platinum nanoparticles in orderedmesoporous carbonrdquo Advanced Healthcare Materials vol 3 no1 pp 36ndash41 2014

[34] J Liu X Hu S Hou et al ldquoAuPt coreshell nanorods withperoxidase- and ascorbate oxidase-like activities for improveddetection of glucoserdquo Sensors and Actuators B Chemical vol166-167 pp 708ndash714 2012

[35] M I Kim M S Kim M-AWoo et al ldquoHighly efficient colori-metric detection of target cancer cells utilizing superior catalyticactivity of graphene oxide-magnetic-platinum nanohybridsrdquoNanoscale vol 6 no 3 pp 1529ndash1536 2014

[36] M Liu H Zhao S Chen H Yu and X Quan ldquoInterface engi-neering catalytic graphene for smart colorimetric biosensingrdquoACS Nano vol 6 no 4 pp 3142ndash3151 2012

[37] Y Ye T Kong X Yu YWu K Zhang and XWang ldquoEnhancednonenzymatic hydrogen peroxide sensing with reducedgraphene oxideferroferric oxide nanocompositesrdquo Talantavol 89 pp 417ndash421 2012

[38] R Cui Z Han and J-J Zhu ldquoHelical carbon nanotubesintrinsic peroxidase catalytic activity and its application forbiocatalysis and biosensingrdquo ChemistrymdashA European Journalvol 17 no 34 pp 9377ndash9384 2011

[39] M Liu H Zhao S Chen H Yu and X Quan ldquoStimuli-responsive peroxidase mimicking at a smart graphene inter-facerdquo Chemical Communications vol 48 no 56 pp 7055ndash70572012

[40] S Liu J Tian L Wang Y Luo and X Sun ldquoA general strategyfor the production of photoluminescent carbon nitride dotsfrom organic amines and their application as novel peroxidase-like catalysts for colorimetric detection of H

2O2and glucoserdquo

RSC Advances vol 2 no 2 pp 411ndash413 2012[41] F Qu T Li and M Yang ldquoColorimetric platform for visual

detection of cancer biomarker based on intrinsic peroxidaseactivity of graphene oxiderdquo Biosensors and Bioelectronics vol26 no 9 pp 3927ndash3931 2011

[42] W Shi QWang Y Long et al ldquoCarbon nanodots as peroxidasemimetics and their applications to glucose detectionrdquo ChemicalCommunications vol 47 no 23 pp 6695ndash6697 2011

[43] X Wang K Qu B Xu J Ren and X Qu ldquoMulticolorluminescent carbon nanoparticles synthesis supramolecularassembly with porphyrin intrinsic peroxidase-like catalyticactivity and applicationsrdquo Nano Research vol 4 no 9 pp 908ndash920 2011

[44] H Wei and E Wang ldquoFe3O4magnetic nanoparticles as per-

oxidase mimetics and their applications in H2O2and glucose

detectionrdquo Analytical Chemistry vol 80 no 6 pp 2250ndash22542008

[45] Q Chang KDeng L ZhuG Jiang C Yu andH Tang ldquoDeter-mination of hydrogen peroxide with the aid of peroxidase-like

10 Journal of Nanomaterials

Fe3O4magnetic nanoparticles as the catalystrdquo Microchimica

Acta vol 165 no 3-4 pp 299ndash305 2009[46] Z Jiang L Kun H Ouyang A Liang and H Jiang ldquoA simple

and sensitive fluorescence quenching method for the determi-nation of H

2O2using rhodamine B and Fe

3O4nanocatalystrdquo

Journal of Fluorescence vol 21 no 5 pp 2015ndash2020 2011[47] Y Jv B Li andR Cao ldquoPositively-charged gold nanoparticles as

peroxidiase mimic and their application in hydrogen peroxideand glucose detectionrdquo Chemical Communications vol 46 no42 pp 8017ndash8019 2010

[48] K Wang J-J Xu D-C Sun H Wei and X-H Xia ldquoSelectiveglucose detection based on the concept of electrochemicaldepletion of electroactive species in diffusion layerrdquo Biosensorsand Bioelectronics vol 20 no 7 pp 1366ndash1372 2005

[49] M I Kim Y Ye B Y Won S Shin J Lee and H G Park ldquoAhighly efficient electrochemical biosensing platform by employ-ing conductive nanocomposite entrapping magnetic nano-particles and oxidase in mesoporous carbon foamrdquo AdvancedFunctional Materials vol 21 no 15 pp 2868ndash2875 2011

[50] M I Kim J Shim T Li J Lee and H G Park ldquoFabrica-tion of nanoporous nanocomposites entrapping Fe

3O4mag-

netic nanoparticles and oxidases for colorimetric biosensingrdquoChemistrymdashAEuropean Journal vol 17 no 38 pp 10700ndash107072011

[51] M I Kim J Shim T Li et al ldquoColorimetric quantificationof galactose using a nanostructured multi-catalyst systementrapping galactose oxidase and magnetic nanoparticles asperoxidasemimeticsrdquoAnalyst vol 137 no 5 pp 1137ndash1143 2012

[52] M I Kim J Shim H J Parab S C Shin J Lee and H G ParkldquoA convenient alcohol sensor using one-pot nanocompositeentrapping alcohol oxidase and magnetic nanoparticles as per-oxidase mimeticsrdquo Journal of Nanoscience and Nanotechnologyvol 12 no 7 pp 5914ndash5919 2012

[53] K S Park M I Kim D-Y Cho and H G Park ldquoLabel-free colorimetric detection of nucleic acids based on target-induced shielding against the peroxidase-mimicking activity ofmagnetic nanoparticlesrdquo Small vol 7 no 11 pp 1521ndash1525 2011

[54] J A Brinkman M Z Rahmani W E Jones A K Chaturvediand M E Hagensee ldquoOptimization of PCR based detection ofhuman papillomavirus DNA from urine specimensrdquo Journal ofClinical Virology vol 29 no 4 pp 230ndash240 2004

[55] L Hafner K Beagley and P Timms ldquoChlamydia trachomatisinfection host immune responses and potential vaccinesrdquoMucosal Immunology vol 1 no 2 pp 116ndash130 2008

[56] M I Kim K S Park and H G Park ldquoUltrafast colorimetricdetection of nucleic acids based on the inhibition of the oxidaseactivity of cerium oxide nanoparticlesrdquo Chemical Communica-tions vol 50 no 67 pp 9577ndash9580 2014

[57] Z Zhang Z Wang X Wang and X Yang ldquoMagneticnanoparticle-linked colorimetric aptasensor for the detection ofthrombinrdquo Sensors and Actuators B Chemical vol 147 no 2 pp428ndash433 2010

[58] B W Blais and A Martinez-Perez ldquoDetection of groupD salmonellae including Salmonella enteritidis in eggs bypolymyxin-based enzyme-linked immunosorbent assayrdquo Jour-nal of Food Protection vol 71 no 2 pp 392ndash396 2008

[59] V Tripathi S Nara S K Chaube et al ldquoDevelopment ofrapid and sensitive one-step direct enzyme linked immunosor-bent assay for 17-120572-OH-progesterone in serumrdquo Journal ofImmunoassay and Immunochemistry vol 29 no 2 pp 117ndash1272008

[60] K DMcReynolds M J Hadd and J Gervay-Hague ldquoSynthesisof biotinylated glycoconjugates and their use in a novel ELISAfor direct comparison ofHIV-1 gp120 recognition ofGalCer andrelated carbohydrate analoguesrdquo Bioconjugate Chemistry vol10 no 6 pp 1021ndash1031 1999

[61] H Hocini S Iscaki J-P Bouvet M D Kazatchkine and LBelec ldquoAn ELISA method to measure total and specific humansecretory IgA subclasses based on selective degradation by IgA1-proteaserdquo Journal of Immunological Methods vol 235 no 1-2pp 53ndash60 2000

[62] L Micheli S Di Stefano D Moscone et al ldquoProduction ofantibodies and development of highly sensitive formats ofenzyme immunoassay for saxitoxin analysisrdquo Analytical andBioanalytical Chemistry vol 373 no 8 pp 678ndash684 2002

[63] L Gao J Wu S Lyle K Zehr L Cao and D Gao ldquoMagnetitenanoparticle-linked immunosorbent assayrdquo Journal of PhysicalChemistry C vol 112 no 44 pp 17357ndash17361 2008

[64] X-Q Zhang S-W Gong Y Zhang T Yang C-YWang andNGu ldquoPrussian blue modified iron oxide magnetic nanoparticlesand their high peroxidase-like activityrdquo Journal of MaterialsChemistry vol 20 no 24 pp 5110ndash5116 2010

[65] Z Tang H Wu Y Zhang Z Li and Y Lin ldquoEnzyme-mimicactivity of ferric nano-core residing in ferritin and its biosensingapplicationsrdquo Analytical Chemistry vol 83 no 22 pp 8611ndash8616 2011

[66] M-A Woo M I Kim J H Jung K S Park T S Seoand H G Park ldquoA novel colorimetric immunoassay utilizingthe peroxidase mimicking activity of magnetic nanoparticlesrdquoInternational Journal of Molecular Sciences vol 14 no 5 pp9999ndash10014 2013

[67] V H C Bramwell G S Doig A B Tuck et al ldquoChangesover time of extracellular domain of HER2 (ECDHER2) serumlevels have prognostic value in metastatic breast cancerrdquo BreastCancer Research andTreatment vol 114 no 3 pp 503ndash511 2009

[68] K S Asgeirsson A Agrawal C Allen et al ldquoSerum epidermalgrowth factor receptor and HER2 expression in primary andmetastatic breast cancer patientsrdquo Breast Cancer Research vol9 no 6 article R75 2007

[69] A Asati C Kaittanis S Santra and J M Perez ldquoPH-tunableoxidase-like activity of cerium oxide nanoparticles achievingsensitive fluorigenic detection of cancer biomarkers at neutralpHrdquo Analytical Chemistry vol 83 no 7 pp 2547ndash2553 2011

[70] K L Fan C Q Cao Y X Pan et al ldquoMagnetoferritinnanoparticles for targeting and visualizing tumour tissuesrdquoNature Nanotechnology vol 7 no 7 pp 459ndash464 2012

[71] S Beatty H-H Koh M Phil D Henson and M BoultonldquoThe role of oxidative stress in the pathogenesis of age-relatedmacular degenerationrdquo Survey of Ophthalmology vol 45 no 2pp 115ndash134 2000

[72] C Korsvik S Patil S Seal and W T Self ldquoSuperoxidedismutase mimetic properties exhibited by vacancy engineeredceria nanoparticlesrdquo Chemical Communications no 10 pp1056ndash1058 2007

[73] E G Heckert A S Karakoti S Seal andW T Self ldquoThe role ofcerium redox state in the SOD mimetic activity of nanoceriardquoBiomaterials vol 29 no 18 pp 2705ndash2709 2008

[74] J Chen S Patil S Seal and J F McGinnis ldquoRare earthnanoparticles prevent retinal degeneration induced by intracel-lular peroxidesrdquo Nature Nanotechnology vol 1 no 2 pp 142ndash150 2006

Journal of Nanomaterials 11

[75] S M Hirst A S Karakoti R D Tyler N Sriranganathan SSeal and C M Reilly ldquoAnti-inflammatory properties of ceriumoxide nanoparticlesrdquo Small vol 5 no 24 pp 2848ndash2856 2009

[76] D-M Huang J-K Hsiao Y-C Chen et al ldquoThe promotion ofhuman mesenchymal stem cell proliferation by superparamag-netic iron oxide nanoparticlesrdquo Biomaterials vol 30 no 22 pp3645ndash3651 2009

[77] N Ding N Yan C Ren and X Chen ldquoColorimetric determi-nation of melamine in dairy products by Fe

3O4Magnetic nano-

particles-H2O2-ABTS detection systemrdquo Analytical Chemistry

vol 82 no 13 pp 5897ndash5899 2010[78] J Zhang J Zhuang L Gao et al ldquoDecomposing phenol by the

hidden talent of ferromagnetic nanoparticlesrdquo Chemospherevol 73 no 9 pp 1524ndash1528 2008

[79] J Z Jiang J Zou L H Zhu L Huang H Jiang and YZhang ldquoDegradation of methylene blue with H

2O2activated

by peroxidase-like Fe3O4magnetic nanoparticlesrdquo Journal of

Nanoscience and Nanotechnology vol 11 no 6 pp 4793ndash47992011

[80] L Gao K M Giglio J L Nelson H Sondermann and AJ Travis ldquoFerromagnetic nanoparticles with peroxidase-likeactivity enhance the cleavage of biological macromolecules forbiofilm eliminationrdquo Nanoscale vol 6 no 5 pp 2588ndash25932014

[81] K Vickery A Pajkos and Y Cossart ldquoRemoval of biofilmfrom endoscopes evaluation of detergent efficiencyrdquo AmericanJournal of Infection Control vol 32 no 3 pp 170ndash176 2004

Submit your manuscripts athttpwwwhindawicom

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CorrosionInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Polymer ScienceInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CeramicsJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CompositesJournal of

NanoparticlesJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

Biomaterials

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

NanoscienceJournal of

TextilesHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Journal of

NanotechnologyHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

CrystallographyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CoatingsJournal of

Advances in

Materials Science and EngineeringHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Smart Materials Research

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MetallurgyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

MaterialsJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Nano

materials

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal ofNanomaterials

Page 10: Review Article Recent Research Trends and Future …downloads.hindawi.com/journals/jnm/2015/756278.pdfnovel biosensor, immunoassay, cancer diagnostics, therapeutics, and environmental

10 Journal of Nanomaterials

Fe3O4magnetic nanoparticles as the catalystrdquo Microchimica

Acta vol 165 no 3-4 pp 299ndash305 2009[46] Z Jiang L Kun H Ouyang A Liang and H Jiang ldquoA simple

and sensitive fluorescence quenching method for the determi-nation of H

2O2using rhodamine B and Fe

3O4nanocatalystrdquo

Journal of Fluorescence vol 21 no 5 pp 2015ndash2020 2011[47] Y Jv B Li andR Cao ldquoPositively-charged gold nanoparticles as

peroxidiase mimic and their application in hydrogen peroxideand glucose detectionrdquo Chemical Communications vol 46 no42 pp 8017ndash8019 2010

[48] K Wang J-J Xu D-C Sun H Wei and X-H Xia ldquoSelectiveglucose detection based on the concept of electrochemicaldepletion of electroactive species in diffusion layerrdquo Biosensorsand Bioelectronics vol 20 no 7 pp 1366ndash1372 2005

[49] M I Kim Y Ye B Y Won S Shin J Lee and H G Park ldquoAhighly efficient electrochemical biosensing platform by employ-ing conductive nanocomposite entrapping magnetic nano-particles and oxidase in mesoporous carbon foamrdquo AdvancedFunctional Materials vol 21 no 15 pp 2868ndash2875 2011

[50] M I Kim J Shim T Li J Lee and H G Park ldquoFabrica-tion of nanoporous nanocomposites entrapping Fe

3O4mag-

netic nanoparticles and oxidases for colorimetric biosensingrdquoChemistrymdashAEuropean Journal vol 17 no 38 pp 10700ndash107072011

[51] M I Kim J Shim T Li et al ldquoColorimetric quantificationof galactose using a nanostructured multi-catalyst systementrapping galactose oxidase and magnetic nanoparticles asperoxidasemimeticsrdquoAnalyst vol 137 no 5 pp 1137ndash1143 2012

[52] M I Kim J Shim H J Parab S C Shin J Lee and H G ParkldquoA convenient alcohol sensor using one-pot nanocompositeentrapping alcohol oxidase and magnetic nanoparticles as per-oxidase mimeticsrdquo Journal of Nanoscience and Nanotechnologyvol 12 no 7 pp 5914ndash5919 2012

[53] K S Park M I Kim D-Y Cho and H G Park ldquoLabel-free colorimetric detection of nucleic acids based on target-induced shielding against the peroxidase-mimicking activity ofmagnetic nanoparticlesrdquo Small vol 7 no 11 pp 1521ndash1525 2011

[54] J A Brinkman M Z Rahmani W E Jones A K Chaturvediand M E Hagensee ldquoOptimization of PCR based detection ofhuman papillomavirus DNA from urine specimensrdquo Journal ofClinical Virology vol 29 no 4 pp 230ndash240 2004

[55] L Hafner K Beagley and P Timms ldquoChlamydia trachomatisinfection host immune responses and potential vaccinesrdquoMucosal Immunology vol 1 no 2 pp 116ndash130 2008

[56] M I Kim K S Park and H G Park ldquoUltrafast colorimetricdetection of nucleic acids based on the inhibition of the oxidaseactivity of cerium oxide nanoparticlesrdquo Chemical Communica-tions vol 50 no 67 pp 9577ndash9580 2014

[57] Z Zhang Z Wang X Wang and X Yang ldquoMagneticnanoparticle-linked colorimetric aptasensor for the detection ofthrombinrdquo Sensors and Actuators B Chemical vol 147 no 2 pp428ndash433 2010

[58] B W Blais and A Martinez-Perez ldquoDetection of groupD salmonellae including Salmonella enteritidis in eggs bypolymyxin-based enzyme-linked immunosorbent assayrdquo Jour-nal of Food Protection vol 71 no 2 pp 392ndash396 2008

[59] V Tripathi S Nara S K Chaube et al ldquoDevelopment ofrapid and sensitive one-step direct enzyme linked immunosor-bent assay for 17-120572-OH-progesterone in serumrdquo Journal ofImmunoassay and Immunochemistry vol 29 no 2 pp 117ndash1272008

[60] K DMcReynolds M J Hadd and J Gervay-Hague ldquoSynthesisof biotinylated glycoconjugates and their use in a novel ELISAfor direct comparison ofHIV-1 gp120 recognition ofGalCer andrelated carbohydrate analoguesrdquo Bioconjugate Chemistry vol10 no 6 pp 1021ndash1031 1999

[61] H Hocini S Iscaki J-P Bouvet M D Kazatchkine and LBelec ldquoAn ELISA method to measure total and specific humansecretory IgA subclasses based on selective degradation by IgA1-proteaserdquo Journal of Immunological Methods vol 235 no 1-2pp 53ndash60 2000

[62] L Micheli S Di Stefano D Moscone et al ldquoProduction ofantibodies and development of highly sensitive formats ofenzyme immunoassay for saxitoxin analysisrdquo Analytical andBioanalytical Chemistry vol 373 no 8 pp 678ndash684 2002

[63] L Gao J Wu S Lyle K Zehr L Cao and D Gao ldquoMagnetitenanoparticle-linked immunosorbent assayrdquo Journal of PhysicalChemistry C vol 112 no 44 pp 17357ndash17361 2008

[64] X-Q Zhang S-W Gong Y Zhang T Yang C-YWang andNGu ldquoPrussian blue modified iron oxide magnetic nanoparticlesand their high peroxidase-like activityrdquo Journal of MaterialsChemistry vol 20 no 24 pp 5110ndash5116 2010

[65] Z Tang H Wu Y Zhang Z Li and Y Lin ldquoEnzyme-mimicactivity of ferric nano-core residing in ferritin and its biosensingapplicationsrdquo Analytical Chemistry vol 83 no 22 pp 8611ndash8616 2011

[66] M-A Woo M I Kim J H Jung K S Park T S Seoand H G Park ldquoA novel colorimetric immunoassay utilizingthe peroxidase mimicking activity of magnetic nanoparticlesrdquoInternational Journal of Molecular Sciences vol 14 no 5 pp9999ndash10014 2013

[67] V H C Bramwell G S Doig A B Tuck et al ldquoChangesover time of extracellular domain of HER2 (ECDHER2) serumlevels have prognostic value in metastatic breast cancerrdquo BreastCancer Research andTreatment vol 114 no 3 pp 503ndash511 2009

[68] K S Asgeirsson A Agrawal C Allen et al ldquoSerum epidermalgrowth factor receptor and HER2 expression in primary andmetastatic breast cancer patientsrdquo Breast Cancer Research vol9 no 6 article R75 2007

[69] A Asati C Kaittanis S Santra and J M Perez ldquoPH-tunableoxidase-like activity of cerium oxide nanoparticles achievingsensitive fluorigenic detection of cancer biomarkers at neutralpHrdquo Analytical Chemistry vol 83 no 7 pp 2547ndash2553 2011

[70] K L Fan C Q Cao Y X Pan et al ldquoMagnetoferritinnanoparticles for targeting and visualizing tumour tissuesrdquoNature Nanotechnology vol 7 no 7 pp 459ndash464 2012

[71] S Beatty H-H Koh M Phil D Henson and M BoultonldquoThe role of oxidative stress in the pathogenesis of age-relatedmacular degenerationrdquo Survey of Ophthalmology vol 45 no 2pp 115ndash134 2000

[72] C Korsvik S Patil S Seal and W T Self ldquoSuperoxidedismutase mimetic properties exhibited by vacancy engineeredceria nanoparticlesrdquo Chemical Communications no 10 pp1056ndash1058 2007

[73] E G Heckert A S Karakoti S Seal andW T Self ldquoThe role ofcerium redox state in the SOD mimetic activity of nanoceriardquoBiomaterials vol 29 no 18 pp 2705ndash2709 2008

[74] J Chen S Patil S Seal and J F McGinnis ldquoRare earthnanoparticles prevent retinal degeneration induced by intracel-lular peroxidesrdquo Nature Nanotechnology vol 1 no 2 pp 142ndash150 2006

Journal of Nanomaterials 11

[75] S M Hirst A S Karakoti R D Tyler N Sriranganathan SSeal and C M Reilly ldquoAnti-inflammatory properties of ceriumoxide nanoparticlesrdquo Small vol 5 no 24 pp 2848ndash2856 2009

[76] D-M Huang J-K Hsiao Y-C Chen et al ldquoThe promotion ofhuman mesenchymal stem cell proliferation by superparamag-netic iron oxide nanoparticlesrdquo Biomaterials vol 30 no 22 pp3645ndash3651 2009

[77] N Ding N Yan C Ren and X Chen ldquoColorimetric determi-nation of melamine in dairy products by Fe

3O4Magnetic nano-

particles-H2O2-ABTS detection systemrdquo Analytical Chemistry

vol 82 no 13 pp 5897ndash5899 2010[78] J Zhang J Zhuang L Gao et al ldquoDecomposing phenol by the

hidden talent of ferromagnetic nanoparticlesrdquo Chemospherevol 73 no 9 pp 1524ndash1528 2008

[79] J Z Jiang J Zou L H Zhu L Huang H Jiang and YZhang ldquoDegradation of methylene blue with H

2O2activated

by peroxidase-like Fe3O4magnetic nanoparticlesrdquo Journal of

Nanoscience and Nanotechnology vol 11 no 6 pp 4793ndash47992011

[80] L Gao K M Giglio J L Nelson H Sondermann and AJ Travis ldquoFerromagnetic nanoparticles with peroxidase-likeactivity enhance the cleavage of biological macromolecules forbiofilm eliminationrdquo Nanoscale vol 6 no 5 pp 2588ndash25932014

[81] K Vickery A Pajkos and Y Cossart ldquoRemoval of biofilmfrom endoscopes evaluation of detergent efficiencyrdquo AmericanJournal of Infection Control vol 32 no 3 pp 170ndash176 2004

Submit your manuscripts athttpwwwhindawicom

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CorrosionInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Polymer ScienceInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CeramicsJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CompositesJournal of

NanoparticlesJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

Biomaterials

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

NanoscienceJournal of

TextilesHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Journal of

NanotechnologyHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

CrystallographyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CoatingsJournal of

Advances in

Materials Science and EngineeringHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Smart Materials Research

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MetallurgyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

MaterialsJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Nano

materials

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal ofNanomaterials

Page 11: Review Article Recent Research Trends and Future …downloads.hindawi.com/journals/jnm/2015/756278.pdfnovel biosensor, immunoassay, cancer diagnostics, therapeutics, and environmental

Journal of Nanomaterials 11

[75] S M Hirst A S Karakoti R D Tyler N Sriranganathan SSeal and C M Reilly ldquoAnti-inflammatory properties of ceriumoxide nanoparticlesrdquo Small vol 5 no 24 pp 2848ndash2856 2009

[76] D-M Huang J-K Hsiao Y-C Chen et al ldquoThe promotion ofhuman mesenchymal stem cell proliferation by superparamag-netic iron oxide nanoparticlesrdquo Biomaterials vol 30 no 22 pp3645ndash3651 2009

[77] N Ding N Yan C Ren and X Chen ldquoColorimetric determi-nation of melamine in dairy products by Fe

3O4Magnetic nano-

particles-H2O2-ABTS detection systemrdquo Analytical Chemistry

vol 82 no 13 pp 5897ndash5899 2010[78] J Zhang J Zhuang L Gao et al ldquoDecomposing phenol by the

hidden talent of ferromagnetic nanoparticlesrdquo Chemospherevol 73 no 9 pp 1524ndash1528 2008

[79] J Z Jiang J Zou L H Zhu L Huang H Jiang and YZhang ldquoDegradation of methylene blue with H

2O2activated

by peroxidase-like Fe3O4magnetic nanoparticlesrdquo Journal of

Nanoscience and Nanotechnology vol 11 no 6 pp 4793ndash47992011

[80] L Gao K M Giglio J L Nelson H Sondermann and AJ Travis ldquoFerromagnetic nanoparticles with peroxidase-likeactivity enhance the cleavage of biological macromolecules forbiofilm eliminationrdquo Nanoscale vol 6 no 5 pp 2588ndash25932014

[81] K Vickery A Pajkos and Y Cossart ldquoRemoval of biofilmfrom endoscopes evaluation of detergent efficiencyrdquo AmericanJournal of Infection Control vol 32 no 3 pp 170ndash176 2004

Submit your manuscripts athttpwwwhindawicom

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CorrosionInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Polymer ScienceInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CeramicsJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CompositesJournal of

NanoparticlesJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

Biomaterials

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

NanoscienceJournal of

TextilesHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Journal of

NanotechnologyHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

CrystallographyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CoatingsJournal of

Advances in

Materials Science and EngineeringHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Smart Materials Research

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MetallurgyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

MaterialsJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Nano

materials

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal ofNanomaterials

Page 12: Review Article Recent Research Trends and Future …downloads.hindawi.com/journals/jnm/2015/756278.pdfnovel biosensor, immunoassay, cancer diagnostics, therapeutics, and environmental

Submit your manuscripts athttpwwwhindawicom

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CorrosionInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Polymer ScienceInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CeramicsJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CompositesJournal of

NanoparticlesJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

Biomaterials

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

NanoscienceJournal of

TextilesHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Journal of

NanotechnologyHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

CrystallographyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CoatingsJournal of

Advances in

Materials Science and EngineeringHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Smart Materials Research

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MetallurgyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

MaterialsJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Nano

materials

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal ofNanomaterials