Au@CuS@CuO2 nanoconstructs self-generate H2O2 and GSH-consuming enhanced CDT combined with PTT for cancer therapy

Chemodynamic therapy (CDT) is a promising therapeutic approach. However, the removal of reactive oxygen species (ROS) by Glutathione (GSH) in tumor cells, insufficient H₂O₂ content and the limitations of single therapy have hindered its better development. Herein, we designed a therapeutic agent Au@CuS@CuO₂ (ACC) that can deplete GSH and generate H₂O₂ at the same time, and has the synergistic therapeutic function of CDT and photothermal therapy (PTT), achieving the accurate and efficient treatment of breast cancer guided by photothermal imaging. Firstly, the CuO₂ shell releases H₂O₂ and Cu²⁺ in the tumor microenvironment (TME), which not only increases the H₂O₂ content in tumor cells but also Cu²⁺ can deplete excessive GSH. Meanwhile, the generated Cu⁺ converts H₂O₂ into highly toxic hydroxyl radical (·OH) through a Fenton-like reaction, achieving efficient CDT. In addition, Au@CuS (AC) under the irradiation of 808 nm laser, not only photothermal imaging can be realized to guide tumor treatment, but also the temperature of the treatment area can be rapidly raised, thereby realize the synergistic therapeutic effect of PTT and CDT. Overall, we have successfully designed and prepared a novel nano-therapeutic agent, achieving significant tumor treatment effects through the synergistic action of CDT/PTT. This study also provides important insights and new ideas for the design and construction of CDT candidate materials with the capabilities of H₂O₂ supply and synergistic treatment systems.