Metal-organic framework-encapsulated nanoparticles for synergetic chemo/chemodynamic therapy with targeted H2O2 self-supply

Nanocatalytic cancer therapy based on chemodynamic therapy, which converts hydrogen peroxide (H2O2) into toxic reactive oxygen species via the Fenton-like reaction, is regarded as a promising therapeutic strategy due to its specific response toward the tumor microenvironment (TME). However, the H2O2 concentration in TME (100 mu M to 1 mM) is insufficient and introducing enough H2O2 or H2O2-generating agents is challenging. In view of this, we report a drug delivery system, CaO2/DOX@Cu/ZIF-8@HA (CDZH), which is capable of targeted H2O2 self-supply and exhibits outstanding chemo/chemodynamic synergetic therapy capability. CaO2/DOX@Cu/ZIF-8@HA is synthesized by fabricating biodegradable Cu/ZIF-8 shell-encapsulated CaO2 nanoparticles, loading chemotherapy drug doxorubicin, and coating a hyaluronic acid shell. In an acidic tumor microenvironment, the CDZH nanostructures targeted the release of doxorubicin, Cu2+, and CaO2. Doxorubicin affects chemotherapy and bioimaging, and CaO2 supplies H2O2 through a Cu-Fenton-like reaction to generate hydroxyl radicals with high oxidation activity for chemodynamic therapy. In brief, the drug delivery system combined targeted H2O2 self-supply and targeted bioimaging possess the potential of an efficient synergistic strategy for chemodynamic therapy and chemotherapy.