pH-responsive nanocatalyst for enhancing cancer therapy via H2O2 homeostasis disruption and disulfiram sensitization

Due to the powerful redox homeostasis and inefficiency of monotherapy, chemodynamic therapy (CDT) is clinically limited. Despite great efforts, the design of CDT nanosystems with specific H2O2 homeostasis and effective integration of multiple treatments remains a great challenge. Therefore, herein, we engineer a novel pH-responsive nanocatalyst to disrupt intracellular H2O2 homeostasis through consuming glutathione (GSH), elevating H2O2 and restraining H2O2 elimination, as well as achieving a combination of CDT and chemotherapy (CT) through sensitized DSF. In the formulation, amplified CDT synergized enhanced CT significantly, strengthening the tumor therapeutic efficacy in vitro and in vivo. This work not only solves intracellular redox homeostasis disruption, but also realizes the re-use of old drugs, providing new insights for CDT-based multimodal cancer therapy.