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

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 x 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.