H2O2-replenishable and GSH-depletive ROS 'bomb' for self-enhanced chemodynamic therapy

Abstract

Chemodynamic therapy (CDT) is an emerging strategy of tumor therapy that utilizes the Fenton reagent to kill tumor cells by disproportionation of H2O2 into hydroxyl radical (OH). However, insufficient endogenous H2O2 confines the antitumor efficacy of CDT. Additionally, the overexpressed glutathione (GSH) exhibits a potent scavenging effect on cytotoxic OH, which further diminishes the efficacy of CDT. Though tremendous efforts have been done, engineering CDT agents with efficient and specific H2O2 self-supplying and GSH-depletion is promising but remains a great challenge. Herein, Fe3+-chelated CaO2 nanoparticles (CaO2-Fe NPs) are constructed as ROS 'bomb'. In the tumor microenvironment, CaO2-Fe NPs can release Fe2+ by the reduction of GSH, and the remaining CaO2 reacts with H+ to selectively generate H2O2. The generated H2O2 can produce OH under the catalysis of Fe2+ through the Fenton reaction, and re-oxidation from Fe2+ to Fe3+ endowing a long-lasting GSH-depletion, resulting in an improved CDT. These CaO2-Fe NPs supply H2O2 and exhaust GSH simultaneously to achieve a self-enhanced CDT, and paves an emerging strategy to enhance the therapeutic efficacy of CDT by combining H2O2-replenishable and GSH-depletive together and realizing a self-enhanced Fenton reaction cycle.