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

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