C60 Fullerene as Synergistic Agent in Tumor-Inhibitory Doxorubicin Treatment

Svitlana Prylutska • Iryna Grynyuk • Olga Matyshevska • Yuriy Prylutskyy • Maxim Evstigneev • Peter Scharff • Uwe Ritter

S. Prylutska 􏰯 I. Grynyuk 􏰯 O. Matyshevska 􏰯 Y. Prylutskyy (&) 􏰯 P. Scharff 􏰯 U. Ritter Joint Ukrainian-German Center on Nanobiotechnology, Kyiv, Ukraine e-mail: prylut@ukr.net S. Prylutska 􏰯 I. Grynyuk 􏰯 O. Matyshevska 􏰯 Y. Prylutskyy Taras Shevchenko National University of Kyiv, Volodymyrska Str., 64, Kyiv 01601, Ukraine M. Evstigneev (&) Department of Biology and Chemistry, Belgorod State University, 85 Pobedy Str., Belgorod 308015, Russia e-mail: max_evstigneev@mail.ru P. Scharff 􏰯 U. Ritter Institute of Chemistry and Biotechnology, Technical University of Ilmenau, Weimarer Str. 25, Ilmenau 098693, Germany

Published online: 12 December 2014 Ó The Author(s) 2014. This article is published with open access at Springerlink.com

Drugs R D (2014) 14:333–340 DOI 10.1007/s40268-014-0074-4

Abstract Background Doxorubicin (Dox) is one of the most potent anticancer drugs, but its successful use is hampered by high toxicity caused mainly by generation of reactive oxygen species. One approach to protect against Dox-dependent chemical insult is combined use of the cytostatic drug with antioxidants. C60 fullerene has a nanostructure with both antioxidant and antitumor potential and may be useful in modulating cell responses to Dox. Objective The aim of this study was to estimate the antitumor effect and antioxidant enzyme activity of com- bined C60 fullerene and Dox (C60 ? Dox) in the liver and heart of mice with Lewis lung carcinoma compared with Dox treatment alone. Methods Highly stable pristine C60 fullerene aqueous colloid solution (concentration 1.0 mg/ml, average hydro- dynamic diameter of nanoparticles 50 nm) was used in the study and characterized by means of atomic force microscopy (AFM). The in vivo investigation of C60-Dox action was performed via the standard methods of histo- logical and enzyme activity analyses. Results Dox (total dose 2.5 mg/kg) combined with C60 fullerene (total dose 25 mg/kg) in tumor-bearing animals resulted in tumor growth inhibition, prolongation of life, metastasis inhibition, and increased number of apoptotic tumor cells and was more effective than the corresponding course of Dox treatment alone. C60 fullerene demonstrated a protective effect against superoxide dismutase and glu- tathione peroxidase inhibition induced by Dox-dependent oxidative insult in the liver and heart. Conclusion Combined treatment with C60 ? Dox is considered to be a promising approach for cancer chemotherapy.

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