Metal-Organic Framework-Assisted Nanoplatform with Hydrogen Peroxide/Glutathione Dual-Sensitive on-Demand Drug Release for Targeting Tumors and Their Microenvironment

Hydrogen peroxide (H2O2)/glutathione (GSH) dual-sensitive nanoplatform holds great promise to alleviate the side effects of chemo drugs and improve the therapeutic efficacy against cancer. The site-specific release of chemotherapeutic drug with low premature release still remains a challenge in the field of chemotherapy. Herein, a novel and multifunctional drug delivery system (DDS) based on polymethylacrylic acid core with cross-linked structure of disulfide bond (PMAABACy), metal-organic framework (MOF) interlayer and biologically inspired polydopamine (PDA) coating was developed, serving as a vehicle for on-demand drug release. The dual-responsive nanoplatform not only prevents the premature leakage of chemotherapeutic drug but also is sensitive to biologically relevant GSH and H2O2 for the precise delivery of chemotherapeutic drug. Considering the transmission route to DDS at the tumor site, the DDS might first respond to the extracellular H2O2 and then to the intracellular GSH, exhibiting a tunable r...