Covalent Organic Framework Nanohydrogel‐Based Oxidase‐Mimicking Nanozyme for Photocatalytic Antibacterial Therapy

Abstract Water‐soluble nanozymes have the potential to overcome the limitations of low catalytic efficiency of most heterogeneous nanozymes in aqueous solutions and further expand their applications in the biomedical field, but with significant synthetic challenges. Here we report an oxidase‐mimicking water‐soluble nanozyme based on zinc porphyrin‐based covalent organic framework nanohydrogel (Zn‐COF‐NHG) for photocatalytic antibacterial. The in situ atom transfer radical polymerization (ATRP) of poly(N‐isopropylacrylamide) (PNIPAM) on scaffold of Zn‐COF results in the exfoliation of crystalline COF nanosheets and assembly into nanohydrogels in aqueous solution. The obtained Zn‐COF‐NHG can effectively mimic photoresponsive oxidase‐like activity for the chromogenic catalysis of 3,3′,5,5′‐tetramethylbenzidine (TMB) by facilitating homogeneous behavior to enhance catalytic efficiency, while also exhibiting intelligent temperature‐response regulation of catalytic oxidation activity. Moreover, the high photodynamic production of reactive oxygen species (ROS) and the reinforcement of binding to the exterior of bacteria through noncovalent interactions concurrently boost its bactericidal activity against Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ) by amplifying oxidative stress. In vivo study on S. aureus ‐infected murine model further substantiates the superior wound disinfection and healing effect of Zn‐COF‐NHG. Our work paves a way for the utilization of COF nanohydrogel as a potent antibacterial nanozyme agent and provides a novel platform for the development of biomedical applications.