Nanozyme with self-fueling and energy-blocking for enhancing reactive oxygen species-mediated tumor therapy by disrupting mitochondrial function

Self-fueling and energy-blocking played important roles in enhancing the antitumor efficacy of reactive oxygen species (ROS) therapy. Here, a novel nanozyme (CuS@Pd/DHA@ZnO 2 ) was constructed by loading dihydroartemisinin (DHA) and coating palladium nanoparticles (PdNPs) and zinc peroxide (ZnO 2 ) on the hollow copper sulfide (CuS), and the enhanced antitumor efficacy was arrived through self-fueling and energy-blocking strategies. In the acidic tumor microenvironment, the ZnO 2 decomposed to produce H 2 O 2 and Zn 2+ , which effectively improved the hydroxyl radicals generation performance of PdNPs and Cu + , and induced the superoxide anion and C-free radicals generation performances by Zn 2+ and Cu 2+ /DHA, resulting in the accumulation of ROS. Moreover, Zn 2+ and ROS storm disrupted synergistically the mitochondrial function, and caused the energy-blocking. Ultimately, by combining the self-fueling and energy-blocking strategies, the tumor growth was almost completely inhibited, demonstrating the excellent antitumor efficacy of CuS@Pd/DHA@ZnO 2 nanozyme.