Synergy of chemo- and photodynamic therapies with C60 fullerene-doxorubicin nanocomplex

Grebinyk, Anna GND; Prylutska, Svitlana; Chepurna, Oksana; Grebinyk, Sergii; Prylutskyy, Yuriy; Ritter, Uwe GND; Ohulchanskyy, Tymish Y. GND; Matyshevska, Olga; Dandekar, Thomas GND; Frohme, Marcus GND

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.

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Grebinyk, A., Prylutska, S., Chepurna, O., Grebinyk, S., Prylutskyy, Y., Ritter, U., Ohulchanskyy, T.Y., Matyshevska, O., Dandekar, T., Frohme, M., 2019. Synergy of chemo- and photodynamic therapies with C60 fullerene-doxorubicin nanocomplex. Nanomaterials: open access journal, Nanomaterials: open access journal 9. 2019, art,1540. https://doi.org/10.3390/nano9111540
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