Protein nanoparticles containing Cu(II) and DOX for efficient chemodynamic therapy via self-generation of H2O2

Chemodynamic therapy (CDT) refers to generating hydroxyl radical (center dot OH) in tumor sites via hydrogen peroxide (H2O2) catalyzed by transition metal ions in cancer cells under acidic environment. However, H2O2 content is not enough for effective CDT, although H2O2 content in cancer cells is higher than that of normal cells. Herein, we synthesized DOX@BSA-Cu NPs (nanoparticles) for effective CDT by providing enhanced content of H2O2 in cancer cells. The results proved Cu2+ in NPs could be reduced to Cu+ by glutathione (GSH) and effectively converted H2O2 to center dot OH. Moreover, the loaded low-dose doxorubicin (DOX) in the NPs could improve the content of H2O2 and resulted in more efficient generation of center dot OH in cancer cells. Thus DOX@BSA-Cu NPs exhibited higher cytotoxicity to cancer cells. This research may provide new ideas for the further studies on more effective Cu(II)-based CDT nanoagents. (C) 2020 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.