Metal–Organic Framework-Derived Active Metal Species for Nanocatalytic Medicine

Metal–organic framework (MOF)-derived active metal species (AMS) have emerged as a versatile nanozyme class, offering tunable catalytic activity through precise control over coordination environments. This Review establishes a three-level structure–activity relationship (SAR) framework linking MOF precursors, pyrolysis-derived active sites, and nanozyme performance. Through systematic cross-study comparisons across peroxidase, oxidase, and antioxidant mechanisms, we demonstrate how atomic coordination engineering—exemplified by Fe–N 4 , Fe–N 4 O 2 , Mo–N 3 , and dual-atom Fe/Co sites—governs catalytic activity, substrate specificity, and ROS regulation. In biomedical applications, we contrast distinct design strategies tailored to pathological microenvironments: photo/thermal-activated platforms for antibacterial therapy, single-atom-driven synergistic systems for cancer nanomedicine, and targeted ROS scavenging for inflammatory and oxidative-stress disorders. Biosafety considerations, including pH-dependent degradation, protein corona effects, and structure–safety design principles, are critically evaluated. Finally, current limitations in scalability, catalytic efficiency, and clinical translation are discussed alongside future opportunities in predictive pyrolysis engineering, standardized activity evaluation, and intelligent microenvironment-responsive therapeutics. This mechanism-driven analysis provides a unified framework for understanding MOF-derived AMS and guides the rational design of next-generation nanozymes.