An Oxidative Stress Nanoamplifier with Efficient Non-Fenton-Type Hydroxyl Radical Generation and Sulfur Dioxide Release for Synergistic Treatment of Tumor

Overcoming tumor antioxidant defenses remains a critical challenge for reactive-oxygen-species-mediated tumor therapies. To address this problem, herein, a theranostic nanomedicine designated as CCM@MIB has been elaborately constructed. Homologous cancer cell membrane (CCM) camouflage significantly enhances the selective accumulation of the nanomedicine at tumor sites. In response to the tumor microenvironment (TME), CCM@MIB controllably releases Mn ions and sulfur dioxide (SO 2 ) molecules. The released Mn ions catalyze the self-oxidation of isoniazid to generate highly toxic •OH, while the SO 2 produced by benzothiazole sulfinate effectively disrupts tumor antioxidant defense systems. The catalase-like activity endowed by Mn ions and the increased intracellular •O 2 – level induced by SO 2 further promote •OH production. Therefore, such an intellectual combination of non-Fenton-type catalytic therapy and SO 2 gas therapy significantly amplifies oxidative stress and efficiently suppresses tumor growth. Additionally, the TME-activated magnetic resonance imaging contrast performance of CCM@MIB is beneficial for guiding antitumor treatment. This considerate strategy designed in our work provides an ingenious paradigm for the development of efficient antitumor therapies.