Michael DubinaCorrespondent Member RAS

Professor Pathophysiology, Oncology, Nanobiothechnology, D.Sci. (Med.)

Biomedical Technologies at Skolkovo: Interdisciplinary

Research Approach

1. Physics of biological processes on atomic level.

2. Structural and functional research of organic and nonorganic substances using accurate technologies and to reveal the mechanisms underlying interconnection of biological characteristics, their atomic structure and features of molecules reciprocal action.

3. Methods to influence biological characteristics of substances on atomic and molecular level.

Biological Goals for Physics Research

1. Multifunctional Effective Personalized Treatment

2. High Quality Nondestructive in vivo Visualisation

3. Sensitive Real-Time Monitoring Diagnostics

4. Novel methods and approaches for research

Medical demand to other disciplines

Cyclotron

Ernest Lawrence

Bragg peak

1971 – «War on Cancer» was declarated by US President Richard Nickson

«War on Cancer»

1900 % 1959 %

Pneumonia and flue 11,8 Heart diseases 38,6

Tuberculosis 11,3 Cancer 15,7

Enteritis 8,3 Stroke 11,5

Heart diseases 8,0 Pneumonia and flue 3,5

Stroke 6,2 Aterosclerosis 2,1

All five causes 35,6 All five causes 71,4

Five leading diseases that caused death in XXth century (Streler B., 1964)

Invasion and metastases

Theories of cancerogenesis and anticancer treatment

Theories:

GENOMICEPIGENOMICVIRAL

Treatment approaches:

SURGICALRADIOTHERAPYCHEMOTHERAPY-------------------------HORMONALTHERAPYIMMUNOTHERAPYTARGET THERAPY

Hanahan D. & Weinberg R.A. The Hallmarks of Cancer // CELL (2000)

Motivation in cancer research

FEARConfusion

Belief

Patient

Oncologists BioTech & Pharm

Knowledge Professionalis

mConfidence

Profit

Society(Government)

Some results of the «War on Cancer»

Cancer Cost More Than Doubled in 40-Year War as Deaths Declined 16 PercentBloomberg News, March 16 (2010)

Steven BenowitzAs War On Cancer Hits 25-Year Mark, Scientists See Progress, Challenges, The Scientist (1996)

U.S. National Cancer Institute (http://seer.cancer.gov)

Year Rate on 100.000 Mortality

1975 59,5 28,1

1985 66,3 26,9

1995 54,0 22,6

2005 46,7 17,4

According the new prognosis, there will be 146 172 newly diagnosed cases of colorectal cancer and 49 920 patients will die from the disease in 2009.

По данным МАИР, за 2000 г. злокачественными опухолями в мире заболело 10 млн. человек. По тем же оценкам, в 2000 г. в мире от рака умерли 8 млн. человек.

Tumor localisation Morbidity Mortality

Lung cancer 1,2 1,1

Breast cancer 1,1 0,4

Colorectal cancer 0,9 0,5

All solid tumors 10,0 8,0

«Cancer on five continents», IARC (WHO), vol 8, 2003

Absolute number of morbidity and mortality in 45 countries during 2000

US National Cancer Institute (NCI) Alliance for Nanotechnology in Cancer

Nanotechnology - science and engineering of manipulating matter at the molecular scale to create devices with novel chemical, physical and biological properties - has the potential to radically change how we diagnose and treat cancer.

Nanotechnology refers to the interactions of cellular and molecular components and engineered materials - typically clusters of atoms, molecules and molecular fragments - at the most elemental level of biology. Such nanoscale objects - typically, though not exclusively, with dimensions smaller than 100 nanometers - can be useful by themselves or as part of larger devices containing multiple nanoscale objects.

http://www.nano.cancer.gov

US National Cancer Institute (NCI) Alliance for Nanotechnology in Cancer

A few examples of promising new Alliance-developed diagnostics and therapies based on nanotechnology. May 2010 Drs. Caius Radu, Owen Witte and Michael Phelps at the Nanosystems Biology Center (Caltech/UCLACCNE) have developed a series of positron emission tomography (PET) imaging agents … are being tested for use in assigning patients for chemotherapy with drugs such as gemcitabine, cytarabine, fludarabine, and others that are used to treat cancers including metastatic breast, non-small cell lung, ovarian, and pancreatic, as well as leukemia and lymphomas.

At the Center of Nanotechnology for Treatment, Understanding, and Monitoring of Cancer (University of California, San Diego, CCNE), Dr. Thomas Kipps has developed a chemically engineered adenovirus nanoparticle to deliver a molecule that stimulates the immune system. Phase I clinical trials, being run jointly by Memgen and the Leukemia & Lymphoma Society, are underway in patients with chronic lymphocytic leukemia (CLL).

Calando Pharmaceuticals, founded by Dr. Mark Davis at the Caltech/UCLACCNE, is conducting clinical trials with a cyclodextrin-based nanoparticle that safely encapsulates a small-interfering RNA (siRNA) agent that shuts down a key enzyme in cancer cells. This open-label, dose-escalating trial is testing the safety of this drug in patients who have become resistant to other chemotherapies.

http://www.nano.cancer.gov

Game of Nature

Function

Proteins

Aminoacids

Nucleotides Notes

Sounds

Accords

Melody

«Negotiations» strategy

Cellular factors of growth, proliferation, differentiation and death

Genetics, biochemistry, metabolome analysis

Ligand – receptor, downstream signaling cascades, intercellular communication

Structure of information flow

Perception and transmission of

information

Interpretation and reproduction of

information

Phenotypic and system manifestation

Proteomics andphysiology

«Sounds»

Structures of«hearing» and «voice»

«hearing and voice»

«Accords and melody»

Academic University

St Petersburg Academic University — Nanotechnology Research and Education Centre of the Russian Academy of Sciences has been founded in 2006 in order to integrate the art of science and education in the field of physics, IT and applied research.

The Chairman of the Centre is the Vice-President of the RAS, a winner of the Nobel Prize in physics (2000) Academician Zhores I. Alferov.

Nanotechnology Facilities and Methods

St Petersburg Physics and Technology Centre for Research and Education RAS 30-04-2008

Industrial-scale molecular beam epitaxy systems: MBE 49 (Riber, France) and GIII (Veeco, USA)

Molecular-beam epitaxy of nanoheterostructures of semiconductor GaAs-based materials.

Growth of III–V heterostructures with quantum dots and their use in optoelectronics, for example in quantum dot lasers.

Epitaxial growth and investigation of nanowhiskers properties.

Theoretical and computer modelling of the growth of semiconductor nanostructures and of their physical properties.

1. Nanoelectrode platforms for bioelectronics to study phenotype changes of cancer cells in vitro.

2. Organic QD for siRNA delivery into cancer cells.

3. Raman spectroscopy for native cDNA to register specific target gene expression in cancer cells without gene amplification.

NBT Lab Researches for Cancer Diagnostics and Treatment

Nanoelectrode platform development for bio-electronic sensor interfaces

Apr. 2010

A3-B5 nanocrystals were developed with radial heterostructures in the following range of parameters: length - 500 nm, diameter 30-50 nm, wavelength 0.7–1.6 microns, surface quantity: 106÷109 cm-2. Spectrophotometric and micropsopy investigations of the nanoheterostructures interactions with different cell lines have been providing using SEM, AFM, Confocal Microscopy.

This research work is supported for 2009-2012 by RAS Presidium Program #27 “Basic research for nanotechnologies and nanomaterials” and RFBR 09-04-12304-OFI-M «Development of the nanobiosensor model on the basis of biolectronics interactions for testing and control of functional status of excitable issues”

PentaLED™ (Rimsa, Italy) Press release. San Jose, CA (February 21, 2003)

First Surgical Lamp with 100% Cold Light and 50,000 - Hour Life, Powered by Lumileds

Advanced LED Technology

•Construction and optic scheme for specialized source of light based on RGB-light emitting diodes has been designed allowing to obtain homogenous and equal 20*20 cm field illumination on 70 cm distance from the source.•Detailed investigation has been conducted for synthesis on different colors light emission with supply current modulation of emitting crystals of the light source•Electrical and optical characteristics of light source. Evaluated nominal and maximal operating conditions.

Grant: Complex interdisciplinary projects by Scientific Center of St.Petersburg programme 2009-2010: St.P.AU-NREC RAS in collaboration with STC for microelectronics and submicrone heterostructures RAS

400 500 600 7000,0

0,2

0,4

0,6

0,8

1,0637

594530Arb.

un

Wavelength, nm

2697K(OL)-2856(AV) 5187K(OL)-4870(AV) 5794K(OL)-6000(AV)

458

ACCULED- 4

Russian LED light sources for surgery lamps

Mission: Investigation and development of new drugs and medical equipment based on nanostructures and nanodevices

Primary goal: to study physical processes in biological systems on nano level and to evaluate the posibility to control substance characteristics on atomic and molecular level.

Purposes: to create research and development center on the base of Saint-Petersburg Academic University. Participation in full cycle of nanobiotechnological research with several scientific fields:

- Physics and Chemistry - Information Technologies - Molecular biology and Genetics - Cytology and Physiology- Clinical Diagnostics - Biostatistics

ProposalsCenter for Research and

Investigations NanoBioPharm