Modulating the local coordination environment of cobalt single-atomic nanozymes for enhanced catalytic therapy against bacteria.

Single-atomic nanozymes (SANZs) characterized by atomically dispersed single metal atoms have recently contributed to breakthroughs in biomedicine due to their satisfactory catalytic activity and superior selectivity compared to their nanoscale counterparts. The catalytic performance of SANZs can be improved by modulating their coordination structure. Therefore, adjusting the coordination number of the metal atoms in the active center is a potential method for enhancing the catalytic therapy effect. In this study, we synthesized various atomically dispersed Co nanozymes with different nitrogen coordination numbers for peroxidase (POD)-mimicking single-atomic catalytic antibacterial therapy. Among the polyvinylpyrrolidone modified single-atomic Co nanozymes with nitrogen coordination numbers of 3 (PSACNZs-N-C) and 4 (PSACNZs-N-C), single-atomic Co nanozymes with a coordination number of 2 (PSACNZs-N-C) had the highest POD-like catalytic activity. Kinetic assays and Density functional theory (DFT) calculations indicated that reducing the coordination number can lower the reaction energy barrier of single-atomic Co nanozymes (PSACNZs-N-C), thereby increasing their catalytic performance. In vitro and in vivo antibacterial assays demonstrated that PSACNZs-N-C had the best antibacterial effect. This study provides proof of concept for enhancing single-atomic catalytic therapy by regulating the coordination number for various biomedical applications, such as tumor therapy and wound disinfection. STATEMENT OF SIGNIFICANCE: The use of nanozymes that contain single-atomic catalytic sites has been shown to effectively promote the healing of bacteria-infected wounds by exhibiting peroxidase-like activity. The homogeneous coordination environment of the catalytic site has been associated with high antimicrobial activity, which provides insight into designing new active structures and understanding their mechanisms of action. In this study, we designed a series of cobalt single-atomic nanozymes (PSACNZs-N-C) with different coordination environments by shearing the Co-N bond and modifying polyvinylpyrrolidone (PVP). The synthesized PSACNZs-N-C demonstrated enhanced antibacterial activity against both Gram-positive and Gram-negative bacterial strains, and showed good biocompatibility in both in vivo and in vitro experiments.