C60(Nd) nanoparticles enhance chemotherapeutic susceptibility of cancer cells by modulation of autophagy.
Autophagy, an evolutionally conserved intracellular process degrading cytoplasmic proteins and organelles for recycling, has become one of the most remarkable strategies applied in cancer research. The fullerene C60 nanoparticle (nC60) has been shown to induce autophagy and sensitize chemotherapeutic killing of cancer cells, but the details still remain unknown. Here we show that a water-dispersed nanoparticle solution of derivatized fullerene C60, C60(Nd) nanoparticles (nC60(Nd)), has greater potential in inducing autophagy and sensitizing chemotherapeutic killing of both normal and drug-resistant cancer cells than nC60 does in an autophagy-dependent fashion. Additionally we further demonstrated that autophagy induced by nC60/C60(Nd) and Rapamycin had completely different roles in cancer chemotherapy. Our results, for the first time, revealed a novel and more potent derivative of the C60 nanoparticle in enhancing the cytotoxicity of chemotherapeutic agents and reducing drug resistance through autophagy modulation, which may ultimately lead to novel therapeutic strategies in cancer therapy.
Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People's Republic of China.
Pengfei
P
Wei
Li
L
Zhang
Yang
Y
Lu
Na
N
Man
Longping
L
Wen
D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D002461:Cell Line, Transformed; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D037741:Fullerenes / Q000494:pharmacology / Q000627:therapeutic use*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D050997:Nanomedicine; D053758:Nanoparticles / Q000627:therapeutic use* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000494:pharmacology; D020123:Sirolimus / Q000494:pharmacology
D037741:Fullerenes; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D017382:Reactive Oxygen Species; D049452:Green Fluorescent Proteins; D004317:Doxorubicin; C069837:fullerene C60; D002945:Cisplatin; D020123:Sirolimus