Mulberry Leaves-Derived Carbon Dots for Photodynamic Treatment of Methicillin-Resistant Staphylococcus aureus-Infected Wounds via Metabolic Perturbation

Antibiotic-resistant pathogens pose a significant global public health challenge, particularly in refractory infections associated with biofilms. The urgent development of innovative, safe, and therapeutically adaptive strategies to combat these resistant biofilms is essential. We present a novel, precise, and controllable photodynamic antibacterial carbon dot (B-M-CD) inspired by the natural antibacterial properties of the mulberry leaf and the bacterial targeting function of boric acid. This photocatalytic antibacterial agent exhibits good biocompatibility and utilizes its inherent antibacterial activities, along with photoactivated oxidase-mimicking activity, to generate reactive oxygen species for the eradication of methicillin-resistant Staphylococcus aureus (MRSA). By leveraging the reversible covalent binding between boronic acid groups and cis-diol groups on bacterial surfaces, we further enhance the targeted antibacterial activity. B-M-CDs effectively penetrate extracellular polymeric substances and demonstrate a precise photodynamic antibacterial effect, allowing for localized delivery aimed at biofilm inhibition and destruction. Metabolomic analyses reveal that B-M-CDs disrupt amino acid metabolism, protein synthesis, electron transport chain, and energy metabolism in MRSA. In vivo experiments confirm that this photocatalyst effectively treats MRSA-induced wounds with an efficacy comparable to that of vancomycin while also exhibiting high biocompatibility. This study represents the first development of a precise, photoactivated, controllable, and targeted carbon-based antibacterial nanozyme derived from the traditional Chinese herb, mulberry leaf, providing a novel strategy for designing intelligent antibacterial nanoagents and underscoring their potential as candidate therapeutics for conditions analogous to MRSA infections.