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

Chemodynamic therapy (CDT) refers to generating hydroxyl radical (^·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 ^·OH. Moreover, the loaded low-dose doxorubicin (DOX) in the NPs could improve the content of H₂O₂ and resulted in more efficient generation of ^·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.