Tumor Microenvironment Cascade Activated Biodegradable Nano-Enzymes for Glutathione-Depletion and Ultrasound-Enhanced Chemodynamic Therapy

Chemodynamic therapy (CDT) is emerged as a novel and promising tumor therapy by using the powerful reactive oxygen species (ROS) to kill cancer cells. However, the current CDT is remarkably inhibited due to insufficient H O supply and over-expression of glutathione (GSH) in the tumor microenvironment (TME). Herein, a biodegradable self-supplying H O nano-enzyme of CuO @CaP with a GSH-consumption effect is designed for cascade enhanced CDT to overcome the problem of H O deficiency and GSH overexpression. In this design, CuO @CaP is gradually degraded to Ca , Cu , and H O in acidic TME, resulting in synergistically enhanced CDT owing to the efficient self-supplied H O and GSH-depletion and Ca overload therapy. Interestingly, the faster degradation of CuO @CaP and promoted production rate of •OH are further achieved after triggering with ultrasound (US). And, the US-enhanced CDT and Ca overload synergistic antitumor therapy is successfully achieved in vivo. These findings provide a promising strategy for designing biodegradable nano-enzymes with self-supplying H O and GSH consumption for US-mediated CDT.