Synergy of Chemo- and Photodynamic Therapies with C60 Fullerene-Doxorubicin Nanocomplex

Nanomaterials

Thomas Dandekar¹  Marcus Frohme²  Anna Grebinyk²  Sergii Grebinyk²  Uwe Ritter³  TymishY. Ohulchanskyy⁴  Oksana Chepurna⁴  Olga Matyshevska⁵  Svitlana Prylutska⁶  Yuriy Prylutskyy⁶ 

[1] Department of Bioinformatics, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, Germany;Division Molecular Biotechnology and Functional Genomics, Technical University of Applied Sciences Wildau, Hochschulring 1, 15745 Wildau, Germany;Institute of Chemistry and Biotechnology, University of Technology Ilmenau, Weimarer Straße 25 (Curiebau), 98693 Ilmenau, Germany;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;Palladin Institute of Biochemistry, NAS of Ukraine, Leontovicha Str. 9, 01030 Kyiv, Ukraine;Taras Shevchenko National University of Kyiv, Volodymyrska 64, 01601 Kyiv, Ukraine;

关键词: photodynamic chemotherapy;    synergistic effect;    c₆₀ fullerene;    doxorubicin;    nanocomplex;    leukemic cells;    apoptosis;   

DOI  :  10.3390/nano9111540

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown