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

Abstract

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 μM 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.