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