Modulating the photodynamic modality of Au22 nanoclusters through surface conjugation of arginine for promoted healing of bacteria-infected wounds

Developing novel antibacterial agents without drug resistance is highly desired but challenging. In this study, an Au nanocluster (NC)-based photodynamic antibacterial agent with aggregation-induced emission (AIE) has been designed to promote the healing of bacteria-infected wounds by conjugating arginine (Arg) on the surface of Au₂₂ NCs. The conjugation of Arg not only endows the NCs with enhanced visible light absorption, increased photoluminescence (PL) intensity, and prolonged PL lifetime, but it also enables switching the photodynamic production mode of reactive oxygen species (ROS) and extra production of reactive nitrogen species (RNS). These enhancements allow the Arg-Au₂₂ NCs to combine ROS/RNS-mediated antibacterial action with the enhanced inherent antibacterial properties of Au NCs, resulting in outstanding antibacterial efficacy against both Gram-negative and Gram-positive bacteria. In vivo experiments demonstrate the effective treatment of bacteria-infected wounds by the Arg-Au₂₂ NCs, leading to the photodynamic eradication of bacterial infections and reduced inflammation in the wound area without causing systemic harm or impairing blood and liver functions. This study introduces a novel approach to designing metal NC-based photodynamic antibacterials with multiple antibacterial actions, contributing to deeper understanding of ROS/RNS-mediated antibacterial mechanisms, and future utilization of metal NCs in antibacterial therapies.