Mechanistic investigation on the toxicity of MgO nanoparticles toward cancer cells

By

N. MOHAMED FAIZEE

13-PCH-19

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Contents

About Nanoparticles

Advantages and disadvantages

Abstract

Introduction

Experimental methods

Result and discussions

Conclusion

References

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What is nanoparticles(NPs)

A nanoparticle (or nanopowder or nanocluster or nanocrystal) is a microscopic

particle with at least one dimension less than 100 nm.

It has large surface area to volume ratio. Nanoparticles exhibit a number of

special properties relative to bulk material.

Color – Nanoparticles of yellow gold and gray silicon are red in color Gold

nanoparticles melt at much lower temperatures (~300 °C for 2.5 nm size) than

the gold slabs (1064 °C)

Absorption of solar radiation in photovoltaic cells is much higher in NPs than it

is in thin films of continuous sheets of bulk material - since the particles are

smaller, they absorb greater amount of solar radiation.

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Why NPs for treating cancer?The NPs guided with a magnet and thus can be localized ina particular part of the body. Thus, it helps to reduce the side effects of cancerdrugs.

The NPs are more easily caught by tumors than by normal tissues.

NPs are very smaller than the blood proteins so that it can easily passes throughthe walls of normal and cancerous cells. Which make them interesting drugcarrier.

High concentration drug getting in to cancerous cells makes them more effectivekilling agent with less side effects.

In Chemotherapy: When you administer the drug it goes everywhere; it killscancer cells, but it also kills healthy cells.

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Other metallic NPs have an effect on both tumor cells and normal human

fibroblasts cells, where as the MgO NPs have an effect on only tumor cells.

The zinc oxide and titanium oxide NPs induced high cytotoxicity in normal

fibroblasts, while magnesium oxide NPs exhibited comparatively low

cytotoxicity on these cells even at high concentrations.

The MgO NPs exhibited low cytotoxicity on normal fibroblasts, and used

to overcome drug resistance in cisplatin-resistant leukemia cancer cells.

The biodegradability and nontoxicity of MgO NPs with their relatively

lightweight properties, excellent thermal properties develop a high-

performance cryosurgery.

Why MgO NPs

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Magnesium oxide NPs are odorless and non-toxic. It possess high hardness,

high purity and a high melting point. Magnesium oxide NPs appears in a

white powder form.

It is used for the production of silicon steel sheet, high-grade ceramic

material, electronic industry material, adhesive and additive in the chemical

raw material

High-frequency magnetic-rod antenna, magnetic device filler, insulating

material filler and various carriers used in radio industry

As a fire retardant used for chemical fiber and plastics trades

Properties and Uses of MgO NPs

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Nanoparticles Antimicrobial mechanism Clinical and industrial

applications

Ag NPs Release of Ag+ ions; disruption of

cell membrane and

electron transport; DNA damage

Dressing for surgical wound

and diabetic foot; coatings for

medical devices.

ZnO NPs Intracellular accumulation of NPs;

cell membrane damage;

H2O2 production; release of Zn2+

ions

Antibacterial creams; lotions

and ointment; surface coating

of medical device.

TiO2 NPs Production of ROS; cell membrane

and wall damage

Antibacterial agent; food

sterilizing agent; air purifiers;

water treatment systems

Au NPs Interaction with cell membranes;

strong electrostatic attraction

Photothermal therapy with

near infrared light, antifungal

agent.

Antimicrobial effects of various NPs

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Advantages of NPs

The use of NPs as delivery vehicles for antimicrobial agents and an effective

therapeutics against many pathogenic bacteria.

NPs-based antimicrobial drug delivery is promising in overcoming resistance to

traditional antibiotics developed by many pathogenic bacteria.

NPs protect drugs from degradation in the body before they reach to the target.

NPs enhances the absorption of drugs into the cancerous cells.

It used for the oncologists to assess the timing and distribution of drugs into the

tissue.

NPs prevent drugs from interacting with normal cells, thus avoiding side effects.

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Advantages and disadvantages of antimicrobial NPs over free antimicrobial agents

Antimicrobial NPs :

Advantage:

• Targeted drug delivery via specific accumulation

• Lowered side effects of chemical antimicrobials

• Extended therapeutic lifetime due to slow elimination

• Controlled drug release

• Broad therapeutic index

• Low cost

Disadvantage:

• High systemic exposure to locally administrated drugs

• Nanotoxicity (lung, kidney, liver, brain, germ cell, metabolic, etc.)

• Lack of characterization techniques.

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Free antimicrobial agents Disadvantage

No specific accumulation

High side effects of chemical antimicrobials

High antimicrobial resistance

Short half life due to fast elimination

Poor solubility

High cost

Advantage

Absence of NPs in the whole body

Absence of nanotoxicity

Well-established characterization techniques

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Other NPs to treat Cancer cells

Gold NPs coated with the drug, which is used to target and kill the cancer

cells.

Gold NPs are non toxic

Gold NPs used to detect the cancer cells and effectively destroy the cancer

cells without affecting the normal cells

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Abstract

Magnesium oxide NPs (MgO NPs) are increasingly recognized for their

applications in cancer therapy such as nano-cryosurgery and hyperthermia.

The present study investigated the cytotoxic effects of magnesium oxide

nanoparticles (MgO NPs) against normal lung fibroblast cells and different

types of cancerous cells. MgO NPs exhibited a preferential ability to kill

cancerous cells such as HeLa, and AGS cells.

To investigate the mechanism of cell death occurring in cancer cells (AGS

cells) by the analysis of morphological changes.

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IntroductionCancer is one of the leading diseases throughout the world in which a group

of cells display uncontrolled growth, invasion, and sometimes metastasis.

The present treatments in cancer therapy, including surgery, radiation,

photodynamic therapy and conventional chemotherapy, but they can affect

all the cells in the body.

The nanosized particles with their size comparable to that of biological

structures are very smart materials for the manipulation, sensing, and

detection of biological systems.

Currently, inorganic nanoparticles for biomedical applications has received

more attention due to their pronounced applications as potential

antibacterial agents, drug delivery vehicles, and in molecular diagnostics

and cancer therapy.

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Experimental methodPreparation of MgO NPs

By

Simple precipitation method

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Mg (NO3)2 (0.1 M) + NaOH (0.2 M) + 50 ml Distilled water

Formation of white precipitate of Mg(OH)2

Mixtures continuous stirring with 2h

Obtained Mg(OH)2 precipitate washed with

distilled water

Dried at 100 ºC and Calcined for 400 ºC

Formation of MgO NPs 16

Mg(NO3)2. 6H2O were dissolved in ethylene glycol solution and Na2CO3

was added into above mixture under sonication. Then it was filtered,

washed using water and dried. Finally, the samples were obtained through

calcination.

MgSO4.7H2O was dissolved in NH4OH and the mixture is constantly

stirring with deionized water and finally dried.

Mg(NO3)2. 6H2O and urea were dissolved in distilled water with

appropriate molar ration and the above mixture under were stirred for 15

min. Then kept at microwave oven. The obtained powder was washed

using distilled water and dried.

Other methods to prepare MgO NPs

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Results and Discussion

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Characterization of MgO NPs

X-ray Diffraction analysis

FT-IR Spectrum

High Resolution Transmission Electron Microscopy – (HR-TEM)

UV– Vis Diffuse reflectance spectroscopy (DRS)

Photoluminescence Spectroscopy (PL)

Raman spectra

Cytotoxicity – Cell Viability Assay

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X-ray diffraction patterns of MgO NPs

The average crystallite size, Debye-

Scherrer formula,

cos

89.0L

L - Average crystallite size (nm)

λ - X-ray wavelength (nm)

β - full width at half maximum (FWHM)

θ - Bragg angle of the plane20

HR-TEM images MgO NPs

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Diffuse reflectance spectra (DRS) of MgO NPs

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FT-IR spectra of MgO NPs

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Raman spectrum of MgO nanoparticles

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Room temperature PL spectra of MgO NPs

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(a) Normal human lung fibroblast CCD-25Lu cells,

(b) HeLa cells,

(c) SNU-16 cells and

(d) AGS cell lines treated for 24, 48 and 72 h respectively.

Cytotoxicity of MgO NPs against various cells

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• The cytotoxicity results of MgO NPs against cancer cells are displayed in the

Figure.

• Fig 4(a) shows that the toxicity of MgO NPs against normal fibroblast cells was

observed even at higher concentrations of MgO (300 g ml⁻1).

• It was evident from Fig. 4(b)–(d) that the cancerous cells were more sensitive to

MgO NPs.

• The figure shows both dose dependent and time dependent toxicity of MgO NPs

towards cancer cells.

• These results suggest that MgO can effectively kill the cancer cells in a dose

dependent manner in 24 h, and only a little difference in toxicity was observed

for 72 h.

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MgO + hv e-cb + h+

vb

(MgO absorbs a photon of energy equal to or greater than its band gap width,

an electron promoted from valence band to the conduction band leaving

behind an electron vacancy or hole in the valence band.

If charge separation is maintained,

O2 + e-cb O2-. (superoxide radical anion)

H2O + h+vb OH. + H+

O2-.and OH. – reactive oxygen species.

Generation of reactive oxygen species (ROS)

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MgO NPs induced apoptosis in AGS cells

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The cells treated with increasing concentrations of MgO NPs showed a

progressive accumulation of the apoptotic bodies (arrows) in a dose and

time dependent manner.

This illustrates the apoptosis mechanism of cell death occurring in

cancerous cells after exposure to MgO NPs.

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ConclusionMgO NPs have been synthesized by a facile, low-cost, simple-precipitationmethod.

MgO NPs are acts as an antimicrobial agent due to its high surface tovolume ratio and unique physico – chemical properties.

The cytotoxicity effects of MgO NPs towards cancer cells are both timeands dose dependent.

MgO NPs are alternative to chemotherapy due to their toxicity levelsagainst cancer cells through apoptosis by ROS generation.

Nanotoxicity depends on electrostatic interaction between NPs withmembrane and accumulation in cytoplasm.

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References

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2871.

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L. Balcells, K. Papazisis, C. Dendrinou, O. Kalogirou , J. Mag. Magn.

Mater. 323 (2011) 780.

[3] M. A. Zolfigol, F. Shirini, G. Chehardoli, E. Kolvari, J. Molecular Catal.

A: Chem., 265 (2007) 272.

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