Abstract
Many diseases are closely associated with abnormal pathological microenvironments, including redox imbalance, hypoxia, weak acidity, elevated H2O2/glutathione (GSH) levels, biofilm formation, and persistent inflammation. Covalent organic framework (COF)-based nanozymes have emerged as promising catalytic nanomedicines owing to their crystalline porous structures, covalently connected skeletons, structural tailorability, tunable pore microenvironments, metal-free design possibilities, and programmable enzyme-like active sites. Applications of COF-based nanozymes in disease therapy have been well documented in the past few years, and there is a need for a systematic summary of structure-activity relationships and translational bottlenecks. This review summarizes recent advances in COF-based nanozymes for disease therapy, focusing on structural features, construction strategies, enzyme-like activities, and therapeutic applications. Key catalytic behaviors, including peroxidase-, oxidase-, catalase-, superoxide dismutase-, glutathione peroxidase-like, and cascade reactions, are discussed in relation to disease microenvironment regulation. Representative applications in cancer therapy, antibacterial and antibiofilm treatment, diabetic wound repair, inflammatory disease modulation, and neuroprotection are highlighted. Finally, current challenges involving structure-activity relationships, catalytic standardization, stability, biosafety, delivery, scalable production, and clinical translation are discussed.