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

A hydrogen peroxide (H2O2)/glutathione (GSH) dual-sensitive nanoplatform holds great promise to alleviate the side effects of chemo drugs and improve their therapeutic efficacy against cancer. The site-specific release of chemo drugs with a low premature release still remains a challenge in the field of chemotherapy. In the present work, a novel and multifunctional drug delivery system (DDS) based on a polymethylacrylic acid core with a 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 a 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 release of chemotherapeutic drug. Through incubation using tumor cells, the growth of tumor cells could be significantly inhibited. Overall, by integrating these different building modules, this research demonstrates the advantages of the MOF-assisted regulate strategy to DDS for a precise site-specific release against tumor cells with a greatly reduced side effect on normal tissues.