C60(Nd) nanoparticles enhance chemotherapeutic susceptibility of cancer cells bymodulation of autophagy

Abstract

Autophagy, an evolutionally conserved intracellular process degrading cytoplasmic proteinsand organelles for recycling, has become one of the most remarkable strategies applied incancer research. The fullerene C60 nanoparticle (nC60) has been shown to induceautophagy and sensitize chemotherapeutic killing of cancer cells, but the details still remainunknown. Here we show that a water-dispersed nanoparticle solution of derivatizedfullerene C60, C60(Nd) nanoparticles (nC60(Nd)), has greater potential in inducingautophagy and sensitizing chemotherapeutic killing of both normal and drug-resistantcancer cells than nC60 does in an autophagy-dependent fashion. Additionally we furtherdemonstrated that autophagy induced by nC60/C60(Nd) and Rapamycin had completelydifferent roles in cancer chemotherapy. Our results, for the first time, revealed a novel andmore potent derivative of the C60 nanoparticle in enhancing the cytotoxicityof chemotherapeutic agents and reducing drug resistance through autophagymodulation, which may ultimately lead to novel therapeutic strategies in cancer therapy.