H2O2-Responsive Nanocatalysts for Synergistic Hydroxyl and Chlorine Radical-Mediated Tumor Therapy

Abstract

Free radicals with reactive chemical properties can combat tumors without inducing drug resistance. Reactive oxygen species (ROS) have been widely applied in tumor therapy; however, the prevalent hypoxic conditions within tumors severely hinder the generation of ROS, leading to suboptimal antitumor efficacy. Herein, we designed an endogenous H2O2-triggered chlorine radical nanogenerator (Cl•) and hydroxyl radicals(•OH), which have better kinetic advantages and higher catalytic activity in catalyzing the H2O2 reaction. In vitro cytotoxicity tests revealed that the nano-urchins induced marked cancer cell death (up to ∼80% at the highest tested concentration) in a concentration-dependent manner, attributable to the chlorine radical-mediated oxidative stress. Moreover, the H2O2-specific activation strategy reduces toxic side effects on normal tissues, thereby enhancing the safety of tumor therapy. Finally, compared with conventional Cu2O nanocatalysts that solely generate •OH, our designed nano-urchins exhibit enhanced therapeutic efficacy, which is mainly attributed to the synergistic therapeutic effect. Therefore, our nano-urchins can serve as a novel nanocatalyst for tumor therapy.