Self-Assembled Copper–Amino Acid Nanoparticles for in Situ Glutathione “AND” H2O2 Sequentially Triggered Chemodynamic Therapy

作者：Baojin Ma, Shu Wang, Feng Liu, Shan Zhang, Jiazhi Duan, Li Zhao, Ying Kong, Yuanhua Sang, Hong Liu, Wenbo Bu, Linlin Li · 发表于：Journal of the American Chemical Society · 年份：2018 · DOI：10.1021/jacs.8b08714 · 被引用次数：1237 · 研究领域：Nanoplatforms for cancer theranostics、Sulfur Compounds in Biology、Lanthanide and Transition Metal Complexes

Nanoformulations that can respond to the specific tumor microenvironment (TME), such as a weakly acidic pH, low oxygen, and high glutathione (GSH), show promise for killing cancer cells with minimal invasiveness and high specificity. In this study, we demonstrate self-assembled copper–amino acid mercaptide nanoparticles (Cu-Cys NPs) for in situ glutathione-activated and H 2 O 2 -reinforced chemodynamic therapy for drug-resistant breast cancer. After endocytosis into tumor cells, the Cu-Cys NPs could first react with local GSH, induce GSH depletion, and reduce Cu 2+ to Cu + . Subsequently, the generated Cu + would react with local H 2 O 2 to generate toxic hydroxyl radicals (·OH) via a Fenton-like reaction, which has a fast reaction rate in the weakly acidic TME, that are responsible for tumor-cell apoptosis. Due to the high GSH and H 2 O 2 concentration in tumor cells, which sequentially triggers the redox reactions, Cu-Cys NPs exhibited relatively high cytotoxicity to cancer cells, whereas normal cells were left alive. The in vivo results also proved that Cu-Cys NPs efficiently inhibited drug-resistant breast cancer without causing obvious systemic toxicity. As a novel copper mercaptide nanoformulation responsive to the TME, these Cu-Cys NPs may have great potential in chemodynamic cancer therapy.