Antibiotic‐Derived Carbon‐Nanodot‐Decorated Hydrogel for Reactive Oxygen Species‐Enhanced Anti‐Infection Through Biofilm Damage

Abstract Irreversible bacterial resistance and impenetrable biofilms have rendered conventional antibiotic therapy ineffective. Nevertheless, increasing evidence has confirmed that antibiotic carbon nanodots (CDs) exhibit potent antibacterial activity. However, the complex chemical composition of antibiotic CDs, and, hence, their antibacterial mechanism, is difficult to understand. The design of new antibiotic CDs against antibacterial resistance is an urgent requirement.In this study, kanamycin‐sulfate‐derived carbon nanodots (KCDs) are found to exhibit significant antibacterial potential with the assistance of light irradiation. Systematic analysis indicates that KCDs not only retain the active structure of kanamycin but also produce five new components modified on its surface, which are shown to inhibit the activity of Staphylococcus aureus beta‐ketoacyl‐acp synthase III (FabH) through molecular docking. Furthermore, the multifunctional hydrogels (CG‐KCDs) self‐assemble into injectable, self‐healing, and antibiofilm structures through noncovalent forces between the KCDs and cationic guar gum (CG). The results indicate that under laser, CG‐KCDs irradiation exhibits enhanced antibacterial activity in vitro by damaging bacterial biofilms in a reactive oxygen species (ROS)‐dependent manner, as determined by transcriptomics. Further, the therapeutic effects of CG‐KCDs hydrogel dressings on wound healing and tissue remodeling under laser are confirmed using an in vivo wound infection model. These results validate the potential of KCDs as efficient antibacterial agents to replace antibiotics as an anti‐infective strategy.