1. Michael Dubina Correspondent Member RAS Professor Pathophysiology, Oncology, Nanobiothechnology, D.Sci. (Med.) Biomedical Technologies at Skolkovo: Interdisciplinary Research Approach

2. 1. P hysics 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 G oals for Physics R esearc h

4. Cyclotron Ernest Lawrence Bragg peak

5. 1971 – «War on Cancer» was d eclarated by US President Richard Nickson «War on C a n cer» Five leading diseases that caused death in XXth century ( Streler B., 1964) 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

6. Invasion and metastases

7. T heories of cancerogenesis and anticancer treatment Theories: GENOMIC EPIGENOMIC VIRAL Treatment approaches: SURGICAL RADIOTHERAPY CHEMOTHERAPY ------------------------- HORMONALTHERAPY IMMUNOTHERAPY TARGET THERAPY Hanahan D. & Weinberg R.A. The Hallmarks of Cancer // CELL (2000)

8. Motivation in cancer research FEAR Confusion Belief Patient Oncologists BioTech & Pharm Knowledge Professionalism C on fidence Profit Society ( Government )

9. Some results of the « War on Cancer » Cancer Cost More Than Doubled in 40-Year War as Deaths Declined 16 Percent Bloomberg News, March 16 (2010) Steven Benowitz As War On Cancer Hits 25-Year Mark, Scientists See Progress, Challenges , The Scientist (1996) U.S. National Cancer Institute (http://seer.cancer.gov) 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. 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

10. 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. «Cancer on five continents», IARC (WHO), vol 8, 2003 Absolute number of morbidity and mortality in 45 countries during 2000 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

11. 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

12. 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

13. Game of Nature Function Proteins Aminoacids Nucleotides Notes Sounds Accords Melody

14. « Negotiations » strategy C ellular 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 and physiology « Sounds » Structures of « hearing » and « voice » « hearing and voice » « Accords and melody »

15. 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 V ice- P resident of the RAS, a winner of the Nobel Prize in physics (2000) Academician Zhores I. Alferov .

16. 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) M olecular-beam epitaxy of nanoheterostructures of semiconductor GaAs-based materials . G rowth of III–V heterostructures with quantum dots and their use in optoelectronics, for example in quantum dot lasers . E pitaxial growth and investigation of nanowhiskers properties . T heoretical and computer modelling of the growth of semiconductor nanostructures and of their physical properties .

17. 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

18. 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: 10 6 ÷10 9 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 ”

19. 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