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

Abstract

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.