Tumor Microenvironment Cascade Activated Biodegradable Nano‐Enzymes for Glutathione‐Depletion and Ultrasound‐Enhanced Chemodynamic Therapy
Xingwang Wen, Chunxia Wang, Shenghui Bi, Yao Xu, Zezheng Wu, Hao Huang, Zhiqiu Liu, Songjun Zeng
Abstract
Abstract 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 2 O 2 supply and over‐expression of glutathione (GSH) in the tumor microenvironment (TME). Herein, a biodegradable self‐supplying H 2 O 2 nano‐enzyme of CuO 2 @CaP with a GSH‐consumption effect is designed for cascade enhanced CDT to overcome the problem of H 2 O 2 deficiency and GSH overexpression. In this design, CuO 2 @CaP is gradually degraded to Ca 2+ , Cu 2+ , and H 2 O 2 in acidic TME, resulting in synergistically enhanced CDT owing to the efficient self‐supplied H 2 O 2 and GSH‐depletion and Ca 2+ overload therapy. Interestingly, the faster degradation of CuO 2 @CaP and promoted production rate of •OH are further achieved after triggering with ultrasound (US). And, the US‐enhanced CDT and Ca 2+ overload synergistic antitumor therapy is successfully achieved in vivo. These findings provide a promising strategy for designing biodegradable nano‐enzymes with self‐supplying H 2 O 2 and GSH consumption for US‐mediated CDT.