Summary: | 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 C<sub>60</sub> fullerene (C<sub>60</sub>) were applied in 1:1 and 2:1 molar ratio, exploiting C<sub>60</sub> 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 C<sub>60</sub>’s extranuclear localization. It gave an opportunity to realize a double hit strategy against cancer cells based on Dox’s antiproliferative activity and C<sub>60</sub>’s photoinduced pro-oxidant activity. When cells were treated with 2:1 C<sub>60</sub>-Dox and irradiated at 405 nm the high cytotoxicity of photo-irradiated C<sub>60</sub>-Dox enabled a nanomolar concentration of Dox and C<sub>60</sub> to efficiently kill cancer cells in vitro. The high pro-oxidant and pro-apoptotic efficiency decreased IC<sub>50</sub> 16, 9 and 7 × 10<sup>3</sup>-fold, if compared with the action of Dox, non-irradiated nanocomplex, and C<sub>60</sub>’s photodynamic effect, correspondingly. Hereafter, a strong synergy of therapy arising from the combination of C<sub>60</sub>-mediated Dox delivery and C<sub>60</sub> photoexcitation was revealed. Our data indicate that a combination of chemo- and photodynamic therapies with C<sub>60</sub>-Dox nanoformulation provides a promising synergetic approach for cancer treatment.
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