标题：Self-Assembled Copper Amino Acid Nanoparticles for in Situ Glutathione "AND" H2O2 Sequentially Triggered Chemodynamic Therapy
作者：Ma, Baojin; Wang, Shu; Liu, Feng; Zhang, Shan; Duan, Jiazhi; Li, Zhao; Kong, Ying; Sang, Yuanhua; Liu, Hong; Bu, Wenbo; Li, Linlin
作者机构：[Ma, Baojin; Liu, Feng; Zhang, Shan; Duan, Jiazhi; Li, Zhao; Kong, Ying; Sang, Yuanhua; Liu, Hong] Shandong Univ, State Key Lab Crystal Mat, Jinan 250 更多
通讯作者：Liu, H;Li, LL;Li, LL;Bu, WB;Bu, WB;Liu, H
通讯作者地址：[Liu, H]Shandong Univ, State Key Lab Crystal Mat, Jinan 250100, Shandong, Peoples R China;[Li, LL]Chinese Acad Sci, Beijing Inst Nanoenergy & Nanosyst 更多
来源：JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
摘要：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 H2O2-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 Cu2+ to Cu+. Subsequently, the generated Cu+ would react with local H2O2 to generate toxic hydroxyl radicals (center dot 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 H2O2 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.