Self-Oxygenated Biomimetic Nanozyme for Tumor Catalytic Immunotherapy

The treatment of solid tumors remains a significant challenge due to the complex, immunosuppressive tumor microenvironment (TME). This manuscript introduces the self-oxygenated biomimetic nanozyme system, SS-MSN@Au-BOM, which innovatively combines catalytic therapy with immunotherapy to modulate the TME for enhanced therapeutic efficacy. Employing mesoporous silicon nanoparticles doped with disulfide bonds, the system integrates gold nanozymes that exhibit glucose oxidase (GOx)-like and peroxidase (POD)-like activities, along with a catalase (CAT) function derived from bacterial outer membrane (BOM) coatings. SS-MSN@Au-BOM significantly disrupted tumor growth by catalyzing endogenous hydrogen peroxide to generate cytotoxic ROS and essential oxygen, enhancing intratumoral ROS levels while alleviating hypoxia. This catalytic action facilitates immunogenic cell death, enhances dendritic cell maturation, and T-cell activation. Notably, the system shows excellent biocompatibility, effective tumor targeting, and prolonged systemic circulation. SS-MSN@Au-BOM offers a dual-functional approach that effectively disrupts the TME and promotes robust antitumor immunity. This study paves the way for further clinical investigation and the development of enzyme-based therapeutics, potentially transforming the landscape of cancer treatment.