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Home Archive 2020 № 3 PREVENTION OF CISPLATIN TOXICITY AGAINST NORMAL CELLS BY COMPLEXATION WITH C60 FULLERENE S. V. Prylutska, I. I. Grynyuk, T. D. Skaterna, L. B. Drobot, N. S. Slobodyanik, O. P. Matyshevska
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ISSN 2410-7751 (Print)
ISSN 2410-776X (Online)

Biotechnologia Acta V. 13, No 3, 2020
Р. 45-51, Bibliography 41, English
Universal Decimal Classification: 615.277.3+615.012]-022.532-092.9


S. V. Prylutska 1, I. I. Grynyuk 1, T. D. Skaterna 2, L. B. Drobot 2, N. S. Slobodyanik 1, O. P. Matyshevska 2

1 Taras Shevchenko National University of Kyiv, Ukraine
2 Palladin Institute of Biochemistry of NAS of Ukraine, Kyiv, Ukraine

The aim of this study was to evaluate the toxicity of noncovalent nanocomplex of C60 fullerene with cisplatin (C60-Cis-Pt) against normal cells. The toxicity of the C60-Cis-Pt nanocomplex compared to the free Cis-Pt was studied by estimating kidney human embryonic (HEK293) cells viability using MTT assay and rat erythrocytes resistance to acid haemolysis. It was shown that free 40 µM Cis-Pt changed the morphology and reduced the viability of HEK293 cells, as well as increased the number of haemolyzed erythrocytes compared to the According to the investigated parameters analysis no cytotoxic effects of C60-Cis-Pt nanocomplex was observed at Cis-Pt equivalent concentration. The prevention of Cis-Pt toxic action against normal cells by its complexation with C60 fullerene opens the prospect of nanostructure usage as an effective cytoprotector and a target carrier in tumor cells..

Key words: C60 fullerene, cisplatin, nanocomplex, НЕК293 cells, cytotoxicity, erythrocytes, haemolysis.

© Palladin Institute of Biochemistry of National Academy of Sciences of Ukraine, 2020

  • References
    • 1. Prylutska S. V., Grebinyk A. G., Lynchak O. V., Byelinska I. V., Cherepanov V. V., Tauscher E., Matyshevska O. P., Prylutskyy Yu. I., Rybalchenko V. K., Ritter U., Frohme M. In vitro and in vivo toxicity of pristine C60 fullerene aqueous colloid solution. Fullerenes, Nanotubes and Carbon Nanostructures. 2019, 27 (9), 715–728.

      2. Franskevych D., Palyvoda K., Petukhov D., Prylutska S., Grynyuk I., Schuetze C., Drobot L., Matyshevska O., Ritter U. Fullerene C60 penetration into leukemic cells and its photoinduced cytotoxic effects. Nanoscale Research Letters. 2017, V. 12, P. 40–49.

      3. Grebinyk A., Grebinyk S., Prylutska S., Ritter U., Matyshevska O., Dandekar T., Frohme M. C60 fullerene accumulation in human leukemic cells and perspectives of LED-mediated photodynamic therapy. Free Radical Biology and Medicine. 2018, V. 124, P. 319–327.

      4. Kolosnjaj J., Szwarc H., Moussa F. Toxicity studies of fullerenes and derivatives. Adv. Exp. Med. Biol. 2007, V. 620, P. 168–180.

      5. Prylutska S. V., Matyshevska O. P., Golub A. А., Prylutskyy Yu. I., Potebnya G. P., Ritter U., Scharff P. Study of С60 fullerenes and С60-containing composites cytotoxicity in vitro. Mater. Sci. Engineer. C. 2007, V. 27, P. 1121–1124.

      6. Tabata Y., Murakami Y., Ikada Y. Photodynamic effect of polyethylene glycolmodified fullerene on tumor. Jpn. J. Cancer Res. 1997, 88 (11), 1108–1116.

      7. Ji Z. Q., Sun H., Wang H., Xie Q., Liu Y., Wang Z. Biodistribution and tumor uptake of C60(OH)x in mice. J. Nanopart. Res. 2006, V. 8, P. 53–63.

      8. Zhu J., Ji Zh., Wang J., Sun R., Zhang X., Gao Y., Sun H., Liu Y., Wang Zh., Li A., Ma J., Wang T., Jia G., Gu Y. Tumor‐inhibitory effect and immunomodulatory activity of fullerol C60(OH)x. Small. 2008, 4 (8), 1168–1175.

      9. Yin J.-J., Lao F., Fu P. P., Wamer W. G., Zhao Y., Wang P.C., Qiu Y., Sun B., Xing G., Dong J., Liang X.-J., Chen C. The scavenging of reactive oxygen species and the potential for cell protection by functionalized fullerene materials. Biomaterials. 2009, 30 (4), 611–621.

      10. Saitoh Y., Ohta H., Hyodo S. Protective effects of polyvinylpyrrolidone-wrapped fullerene against intermittent ultraviolet-A irradiation-induced cell injury in HaCaT cells. J. Photochem. Photobiol. B. 2016, V. 163, P. 22‒29.

      11. Yamakoshi Y., Umezava N., Ryu A., Arakane K., Miyata N., Goda Y., Masumizu T., Nagano T. Active oxygen species generated from photoexited fullerene (C60) as potential medicines: О2.- versus 1O2. J. Chem. Soc. 2003, V. 125, P. 12803‒12809.

      12. Huang Y.-Y., Sharma S. K., Yin R., Agrawal T., Chiang L. Y., Hamblin M. R. Functionalized fullerenes in photodynamic therapy. J. Biomed. Nanotechnol. 2014, 10 (9), 1918–1936.

      13. Moor K. J., Snow S. D., Kim J. H. Differential photoactivity of aqueous [C60] and [C70] fullerene aggregates. Environ. Sci Technol. 2015, V. 49, P. 5990–5998.

      14. Mroz P., Pawlak А., Satti M., Lee H., Wharton T., Gali H. Sarna T., Hamblin M. R. Functionalized fullerenes mediate photodynamic killing of cancer cells: Type I versus Type II photochemical mechanism. Free Radic. Biol. Med. 2007, V. 43, P. 711–719.

      15. Zakharian T. Y., Seryshev A., Sitharaman B., Gilbert B. E., Knight V., Wilson L. J. A Fullerene-paclitaxel chemotherapeutic: Synthesis, characterization, and study of biological activity in tissue culture. J. Am. Chem. Soc. 2005, V. 127, P. 12508–12509.

      16. Chaudhuri P., Paraskar A., Soni S., Mashelkar R. A., Sengupta S. Fullerenol cytotoxic conjugates for cancer chemotherapy. ASC Nano. 2009, 3 (9), 2505–2514.

      17. Lu F., Haque S. A., Yang S. T., Luo P. G., Gu L., Kitaygorodskiy A., Li H., Lacher S., Sun Y.-P. Aqueous compatible fullerene-doxorubicin conjugates. J. Phys. Chem. C. 2009, 113 (41), 17768–17773.

      18. Berndtsson M., Heagg M., Panaretakis T., Havelka A. M., Shoshan M. C., Linder S. Acute apoptosis by cisplatin requires induction of reactive oxygen species but is not associated with damage to nuclear DNA. Int. J. Cancer. 2007, 120 (1), 175–180.

      19. Cepeda V., Fuertes M. A., Castilla J., Alonso C., Quevedo C., Pérez J. M. Biochemical Mechanisms of Cisplatin Cytotoxicity. Anticancer. Agents Med. Chem. 2007, 7 (1), 3–18.

      20. Pratibha R., Sameer R., Rataboli P. V., Bhiwgade D. A., Dhume C. Y. Enzymatic studies of cisplatin induced oxidative stress in hepatic tissue of rats. Eur. J. Pharmacol. 2006, V. 532, P. 290–293.

      21. Florea A.-M., Buesselberg D. Cisplatin as an Anti-Tumor Drug: Cellular Mechanisms of Activity, Drug Resistance and Induced Side Effects. Cancers (Basel). 2011, 3 (1), 1351–1371.

      22. Galluzzi L., Vitale І., Michels J., Brenner C., Szabadkai G., Harel-Bellan A., Castedo M., Kroemer G. Systems biology of cisplatin resistance: past, present and future. Cell Death Dis. 2014, 5 (5), 1–18.

      23. Prylutska S. V., Lynchak O. V., Kostjukov V. V., Evstigneev M. P., Remeniak O. V., Rybalchenko V. K., Prylutskyy Yu. I., Ritter U., Scharff P. Antitumor effects and hematotoxicity of С60-Cis-Pt nanocomplex in mice with Lewis lung carcinoma. Exp. Oncol. 2019, 41 (2), 106–111.

      24. Golub O., Matyshevska S., Prylutska V., Sysoyev L., Ped V., Kudrenko E., Radchenko Yu., Prylutskyy P., Scharff T. Braun. Fullerenes immobilized at silica surface: topology, structure and bioactivity. J. Mol. Liq. 2003, 105 (2‒3), 141–147.

      25. Schuetze C., Ritter U., Scharff P., Bychko A., Prylutska S., Rybalchenko V., Prylutskyy Yu. Interaction of N-fluorescein-5-isothiocyanate pyrrolidine-C60 compound with a model bimolecular lipid membrane. Mater. Sci. Engineer. C. 2011, 31 (5), 1148–1150.

      26. Prylutska S. V., Grynyuk I. I., Skaterna T. D., Horak I. R., Grebinyk A. G., Drobot L. B., Matyshevska O. P., Senenko A. I., Prylutskyy Yu. I., Naumovets A. G., Ritter U., Frohme M. Toxicity of C60 fullerene-сisplatin nanocomplex against Lewis lung carcinoma cells. Arch. Toxicol. 2019, 93 (5), 1213–1226.

      27. Mosunov A., Evstigneev V., Buchelnikov A., Salo V., Prylutskyy Y., Evstigneev M. General up-scaled model of ligand binding with C60 fullerene clusters in aqueous solution. Chemical Physics Letters. 2019, V. 721, P. 22–26.

      28. Carmichael J., Degraff W. G., Gazdar A. F., Minna J. D., Mitchell J. B. Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. Cancer Res. 1987, V. 47, P. 936–942.

      29. Terskov I. A., Gitelzon I. I. Method of chemical (acid) erythrograms. Biofizika. 1957, 2 (2), 259–266 (In Russian).

      30. Liu S., Liu H., Yin Z., Guo K., Gao X. Cytotoxicity of pristine C60 fullerene on baby hamster kidney cells in solution. J. Biomater. Nanobiotechnol. 2012, 3 (3), 385–390.

      31. Atilano-Roque A., Wen X., Aleksunes L. M., Joy M. S. Nrf2 activators as potential modulators of injury in human kidney cells. Toxicol Rep. 2016, V. 3, P. 153–159.

      32. Gharbi N., Pressac M., Hadchouel M., Szwarc H., Wilson S. R., Moussa F. C60 fullerene is a powerful antioxidant in vivo with no acute or subacute toxicity. Nano Lett. 2005, V. 5, P. 2578–2585.

      33. Ferreira C. A., Ni D., Rosenkrans Z. T., Cai W. Scavenging of reactive oxygen and nitrogen species with nanomaterials. Nano Res. 2018, V. 11, P. 4955–4984.

      34. Grynyuk I., Grebinyk S., Prylutska S., Mykhailova A., Franskevich D., Matyshevska O., Schütze C., Ritter U. Photoexcited fullerene C60 disturbs prooxidant-antioxidant balance in leukemic L1210 cells. Mat.-wiss. und Werkstofftech. 2013, 44 (2–3), 139–143.

      35. Prylutska S. V., Grynyuk I. I., Grebinyk S. M., Matyshevska O. P., Prylutskyy Y. I., Ritter U., Siegmund C., Scharff P. Сomparative study of biological action of fullerenes C60 and carbon nanotubes in thymus cells. Mat.-wiss. und Werkstofftech. 2009, V. 40, P. 238–241.

      36. Franskevych D. V., Grynyuk I. I., Prylutska S. V., Matyshevska O. P. Modulation of cisplatin-induced reactive oxygen species production by fullerene C60 in normal and transformed lymphoid cells. Ukr. Biochem. J. 2016, V. 88, P. 44–50.

      37. Kutwin M., Sawosz E., Jaworski S. Structural damage of chicken red blood cells exposed to platinum nanoparticles and cisplatin. Nanoscale Res. Lett. 2014, 9 (1), 257–283.

      38. Suwalsky M., Hernández P., Villena F., Sotomayor C. P. The anticancer drug cisplatin interacts with the human erythrocyte membrane. Z. Naturforsch. C J. Biosci. 2000, 55 (5‒6), 461–466.

      39. Rebillard A., Lagadic-Gossmann D., Dimanche-Boitrel M. T. Cisplatin cytotoxicity: DNA and plasma membrane targets. Curr. Med. Chem. 2008, 15 (26), 2656–2663.

      40. Prylutska S. V., Grynyuk I. I., Golub А. A., Matyshevska O. P. Evaluation of cytotoxicity parameters of C60 and C60-containing composites in vitro. Dopov. Nac. akad. nauk Ukr. 2006, N 1, P. 163‒167 (In Ukrainian).

      41. Rozhkov S. P., Goryunov A. S., Sukhanova G. A., Borisova A. G., Rozhkova N. N., Andrievsky G. V. Protein interaction with hydrated C60 fullerene in aqueous solutions. Biochem. Biophys. Res. Commun. 2003, V. 303, P. 562–566.


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Home Archive 2020 № 3 PREVENTION OF CISPLATIN TOXICITY AGAINST NORMAL CELLS BY COMPLEXATION WITH C60 FULLERENE S. V. Prylutska, I. I. Grynyuk, T. D. Skaterna, L. B. Drobot, N. S. Slobodyanik, O. P. Matyshevska

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