Details

Autor(en) / Beteiligte

• Ma, Baojin
• Wang, Shu
• Liu, Feng
• Zhang, Shan
• Duan, Jiazhi
• Li, Zhao
• Kong, Ying
• Sang, Yuanhua
• Liu, Hong
• Bu, Wenbo
• Li, Linlin

Titel

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

Ist Teil von

• Journal of the American Chemical Society, 2019-01, Vol.141 (2), p.849-857

Ort / Verlag

American Chemical Society

Erscheinungsjahr

2019

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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 (·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.