Synergy of Chemo- and Photodynamic Therapies with C<sub>60</sub> Fullerene-Doxorubicin Nanocomplex
Anna Grebinyk,
Svitlana Prylutska,
Oksana Chepurna,
Sergii Grebinyk,
Yuriy Prylutskyy,
Uwe Ritter,
Tymish Y. Ohulchanskyy,
Olga Matyshevska,
Thomas Dandekar,
Marcus Frohme
Affiliations
Anna Grebinyk
Division Molecular Biotechnology and Functional Genomics, Technical University of Applied Sciences Wildau, Hochschulring 1, 15745 Wildau, Germany
Svitlana Prylutska
Taras Shevchenko National University of Kyiv, Volodymyrska 64, 01601 Kyiv, Ukraine
Oksana Chepurna
Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China
Sergii Grebinyk
Division Molecular Biotechnology and Functional Genomics, Technical University of Applied Sciences Wildau, Hochschulring 1, 15745 Wildau, Germany
Yuriy Prylutskyy
Taras Shevchenko National University of Kyiv, Volodymyrska 64, 01601 Kyiv, Ukraine
Uwe Ritter
Institute of Chemistry and Biotechnology, University of Technology Ilmenau, Weimarer Straße 25 (Curiebau), 98693 Ilmenau, Germany
Tymish Y. Ohulchanskyy
Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China
Olga Matyshevska
Palladin Institute of Biochemistry, NAS of Ukraine, Leontovicha Str. 9, 01030 Kyiv, Ukraine
Thomas Dandekar
Department of Bioinformatics, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, Germany
Marcus Frohme
Division Molecular Biotechnology and Functional Genomics, Technical University of Applied Sciences Wildau, Hochschulring 1, 15745 Wildau, Germany
A nanosized drug complex was explored to improve the efficiency of cancer chemotherapy, complementing it with nanodelivery and photodynamic therapy. For this, nanomolar amounts of a non-covalent nanocomplex of Doxorubicin (Dox) with carbon nanoparticle C60 fullerene (C60) were applied in 1:1 and 2:1 molar ratio, exploiting C60 both as a drug-carrier and as a photosensitizer. The fluorescence microscopy analysis of human leukemic CCRF-CEM cells, in vitro cancer model, treated with nanocomplexes showed Dox’s nuclear and C60’s extranuclear localization. It gave an opportunity to realize a double hit strategy against cancer cells based on Dox’s antiproliferative activity and C60’s photoinduced pro-oxidant activity. When cells were treated with 2:1 C60-Dox and irradiated at 405 nm the high cytotoxicity of photo-irradiated C60-Dox enabled a nanomolar concentration of Dox and C60 to efficiently kill cancer cells in vitro. The high pro-oxidant and pro-apoptotic efficiency decreased IC50 16, 9 and 7 × 103-fold, if compared with the action of Dox, non-irradiated nanocomplex, and C60’s photodynamic effect, correspondingly. Hereafter, a strong synergy of therapy arising from the combination of C60-mediated Dox delivery and C60 photoexcitation was revealed. Our data indicate that a combination of chemo- and photodynamic therapies with C60-Dox nanoformulation provides a promising synergetic approach for cancer treatment.
