O.A. Lopatina - Ph.D.(Med.), Leading Research Scientist, Federal Research N.F Gamaleya Center of Epidemiology and Microbiology D.I. Ivanovsky Institute of Virology O.V. Baklanova - Ph.D.(Biol.), Senior Research Scientist, Federal Research N.F Gamaleya Center of Epidemiology and Microbiology D.I. Ivanovsky Institute of Virology I.A. Suetina - Ph.D.(Biol.), Leading Research Scientist, Federal Research N.F Gamaleya Center of Epidemiology and Microbiology D.I. Ivanovsky Institute of Virology G.R. Mikhailova - Ph.D.(Biol.), Leading Research Scientist, Federal Research N.F Gamaleya Center of Epidemiology and Microbiology D.I. Ivanovsky Institute of Virology E.A. Guchina - Ph.D.(Biol.), Leading Research Scientist, Federal Research N.F Gamaleya Center of Epidemiology and Microbiology D.I. Ivanovsky Institute of Virology F.A. Lisicin - Ph.D.(Biol.), Leading Research Scientist, Federal Research N.F Gamaleya Center of Epidemiology and Microbiology D.I. Ivanovsky Institute of Virology L.I. Russu - Research Scientist, Federal Research N.F Gamaleya Center of Epidemiology and Microbiology D.I. Ivanovsky Institute of Virology S.A. Kovalevskyi Junior Research Scientist, N.N. Semenov Institute of Chemical Physics, RAS B.A. Budanov - Dr.Sc.(Phys.-Math.), Professor, N.N. Semenov Institute of Chemical Physics, RAS F.I. Dalidchik - Dr.Sc.(Phys.-Math.), N.N. Semenov Institute of Chemical Physics, RAS M.V. Mezentzeva - Dr.Sc.(Biol.), Federal Research N.F Gamaleya Center of Epidemiology and Microbiology D.I. Ivanovsky Institute of Virology

Polyoxometalates (POMs) are stable metal-oxide inorganic compounds. Their structure and electronic properties can be modified. They are one of the perspective products of nanotechnology in medicine and bioengineering, in-cluding antiviral and antitumor drug development. In this context, it is required to investigate POM-s cytotoxity on cells culture. Objective: to investigate biological processes of different POM samples on cells culture: human embryo fibroblast (HEF), human lung embrio (HLE) and human lung carcinoma A-549. POM cytotocxic effect on HEF cell was investigated by MTT-test. Growth activity was measured by proliferative index and cells vitality. Cells morphology was investigated by atomic-force (AFM) and electron microscopes (EM). Results: POM samples demonstrated various toxic effects on cells cultures. POMs (H3PW12O40, H4SiMo12O40. H3PMo12O4 ) reduced cells growth activity and led to significant morphology changes, seen in AFM and EM. Cells destruction and deterioration with failure of cytoplasm membrane structures and karyolysis, up to cells necrosis. Comparison between proliferation index and reduction potential after the 4th passage of HLE cells was realized. Correlation between proliferation index and reduction potential also was found. The most toxic samples were POM A - H3PW12O40 and POM C - H4SiW12O40. They had the lowest reduction potential. It was identified that IC50 se-quence corresponded reduction potentials. It provides the possible ways for potential medicine creation.

 

1. Pope M. T.Heteropoly and IsopolyOxometalates. Berlin: SpringerVerlag. 1983.
2. Rhule J.T., Hill C.L., Judd D.A. et.al. Polyoxometalates in medicine // Chem. Rev. 1998. V.98. P.327 - 358.
3. Shigeta S., Mori S., Yamase T. et. al. Anti-RNA virus activity of polyoxometalates // Biomed. Pharmacother. 2006.  V. 60. P.211 - 219.
4. Hosseini S.M., Amini E., Kheiri M.T. et.al.  Anti-influenza Activity of a Novel Polyoxometalate Derivative (POM-4960) // Int. J. Mol. Cell. Med. Winter. 2012. V.1. № 1. P.21.
5. Mirzojan A.F. Protivovirusnaja interferonogennaja aktivnost novogo polioksimetallata: Avtoref. kand. biol. nauk. Erevan. 2013.
6. Yanagie H., Ogata A., Mitsui S. et al. Anticancer activity of polyoxomolybdate // Biomed. Pharmacother. 2006. V. 60. P.349 - 352.
7. Wang Lu, Zhou Baibin, Liu Jiaren.Anticancer Polyoxometalates // Progress in Chemistry. 2013. V. 25. P. 1131 - 1141. 
8. Wang X., Liu J., Li J., Yang Y., Liu J., Li B., Pope M. T. J. Synthesis and antitumor activity of cyclopentadienyltitanium substituted polyoxotungstate [CoW₁₁₀O₃₉ (CpTi)]_7t (Cp=I-O3 ₅?C₅H₅) // Inorg. Biochem. 2003. V. 94.  P. 279 - 284.
9. Ivanka Holclajtner-Antunovic and et.al. Study of some Polyoxometalates of Keggins type as potential antitumour agent // Jugoslov. MedBiochem. 2004. V. 23. P. 25 - 30.
10. Podchernjaeva R.JA., Suetina I.A., Mikhajjlova G.R., Lopatina O.A., Bobrineckijj I.I., Morozov R.A., Seleznev A.S. Kultivirovanie perevivaemykh kletochnykh linijj na podlozhkakh iz uglerodnykh nanotrubok i vlijanie ehlektrostimuljacii na proliferaciju kletok // Voprosy virusologii. 2012. T. 57. № 5. S. 46 - 48.
11. Suetina I.A., Podchernjaeva R.JA., Lopatina O.A.,  Ostroumov S.A. Toksikologija nanomaterialov: ocenki toksichnosti nanochastic okislov medi i zheleza na kulture kletok // Nanomaterialy i nanotekhnologii v zhivykh sistemakh. Bezopasnost i nanomedicina. M.: ROSNANO. 2011. S. 91.
12. Djakonov L.D. ZHivaja kletka v kulture (metody i primenenija v biologii). M. 2009. C. 231 - 245.
13. Jing B., Zhu Y., Hutin M., Cronin L. Polyoxometalate macroion induced phase and morphology instability of lipid membrane // Chem. Sci. 2013. V. 4. P. 3818
14. Mori H., Mizuno N., Misono M. Factors controlling the selectivity of the oxidation of acetaldehyde over heteropoly compounds // J. Catal. 1990. V. 131. P. 133 - 142.
15. Song I., Barteau M. Redox properties of Keg­gin-type heteropolyacid (HPA) catalysts: effect of counter-cation, heteroatom, and polyatom substitution // J. Molec. Catal. 2004. V. A: 212. P. 229.
16. Yamase T., Tomita K., Sato Y., Fujita H. Antitumour and Antivirus Activities of a Curtain Polyoxometalates, Polimer in Medicine: Boimedical and Pharmaceutical Applications // Technomic Pub. Company Inc. Lancaster 1992. Chapter 13. P. 187 - 212
17. Jurgensen A., Moffat J.B. The stability of 12-molybdo­silicic, 12-tungstosilicic, 12-molybdophosphoric and 12-tu­ngstophosphoric acids in aqueous-solution at various PH // Catal. Lett. 1995. V. 34. P. 237.