Engineered Nanozymes for Enhanced Anti-Inflammatory Therapy

Persistent oxidative stress and inflammation are key pathogenic features of chronic inflammatory diseases, driving immune dysregulation and progressive tissue damage. Although reactive oxygen species (ROS) serve as significant mediators in cellular signaling and biological function regulation, their pathological overaccumulation leads to biomolecular damage and exacerbates inflammatory cascades. Current antioxidant strategies, whether endogenous or exogenous, suffer from limitations including poor stability, high costs, imprecise targeting, and suboptimal therapeutic efficacy. Nanozymes, which combine catalytic properties with nanoscale tunability, offer a solution through a “targeting-catalysis synergy” paradigm, moving beyond the mere sum of their parts. This review systematically explored this paradigm by (1) cataloging the “catalytic toolbox” (superoxide dismutase (SOD), catalase (CAT), peroxidase (POD) mimics) available for ROS regulation; (2) analyzing how advanced targeting strategies (membrane camouflage, surface functionalization, covalent conjugation, hydrogel loading, liposomal encapsulation) act as a crucial link to spatially localize catalytic activity within inflammatory sites; and (3) demonstrating how this synergy is operationalized to achieve superior outcomes in chronic inflammatory diseases (atherosclerosis (AS), inflammatory bowel disease (IBD), rheumatoid arthritis (RA), osteoarthritis (OA)). Finally, we critically assessed the translational challenges and opportunities from the perspective of this synergistic paradigm, outlining a path for future nanozyme design.