Antimicrobial Nanozymes: Structure–Activity-Guided Design, Synergy, and Applications

Nanozymes are emerging as versatile antimicrobial agents to tackle drug-resistant infections and biofilm-associated persistence. In this review, we present an integrated framework that links natural enzyme-mediated host defense to the rational development of antimicrobial nanozymes, and summarize recent advances through a mechanism-materials-engineering-application pipeline. We first summarize representative bactericidal principles of natural enzymes to highlight bioinspired catalytic motifs relevant to nanozyme design. We then classify antibacterial nanozymes by catalytic reaction types, including oxidoreductase- and hydrolase-like activities, and by material platforms, highlighting structure-activity relationships that govern catalytic behavior and antimicrobial performance. Building on these mechanistic and structural insights, we summarize engineering-enhanced bactericidal modalities, including photothermal and photodynamic assistance, metal ion release, immune modulation, cascade catalysis, microenvironment-responsive regulation, and targeting, that help overcome constraints imposed by infectious microenvironments, such as hypoxia, limited hydrogen peroxide availability, elevated antioxidant levels, and biofilm barriers. Finally, we translate these principles into application-oriented guidance across interfaces ranging from abiotic surface protection, including antifouling and device coatings, to superficial and deep-seated infections, and we briefly discuss emerging nanozyme strategies for antifungal and antiviral interventions. Throughout, we emphasize translational considerations, such as activity benchmarking, biosafety evaluation, and scalable manufacturing, to support the development of clinically relevant antimicrobial nanozymes.