Synergetic antineoplastic action of doxorubicin and fullerene C60 as means of its delivery towards human cancer cells in vitro: cellular and molecular mechanisms

Abstract

Development of new pharmaceutical formulations based on using specific nano­scale carriers for improved drug delivery to target cells is one of crucial tasks of current pharmaceutics. Usage of such nanocomposites does not only extend the duration of action of drugs in the organism of patients, but also increases their bioavailability and, most importantly, reduces side effects of chemotherapy. We used nanocomplex based on fullerene C60 and well-known anticancer drug doxorubicin (Dx). It was found that immobilization of doxorubicin on fullerene C60 leads to 2–3 fold increase of the antineoplastic action of this drug in vitro towards various tumor cell lines compared with the effect of free doxorubicin. Cytomorphological studies have shown that the death of these tumor cells treated with this nanocomplex, occurs by apoptosis. Apoptosis induction by the action of C60-Dx complex is accompanied by the generation of superoxide radicals whose level increases significantly as soon as at the 1st hour after addition of this complex and reaches a maximum value in 3 hours. The obtained results suggest a prospectivity of application of fullerene-C60-doxorubicin complex in chemotherapy of malignant tumors.

Keywords

• fullerene с60
• doxorubicin
• nanocomplex
• reative oxygen species
• apoptosis
• cancer drug resistance