Visible-light-responsive cationized photodynamic nanoparticles integrated with a silk fibroin-based nanofibrous matrix for enhanced ROS utilization in infected wound healing

Drug-resistant bacteria infecting wounds and impeding their healing have become a pressing clinical challenge. Antimicrobial photodynamic therapy (aPDT) does not pose a risk of bacterial resistance, but its application is limited due to the short lifespan, restricted diffusion distance, and non-selective biological toxicity of reactive oxygen species (ROS). Herein, we developed a visible-light-responsive organic nanoplatform (iTPyPXs/SCM) that improves ROS utilization for antimicrobial therapy while limiting excessive intracellular ROS. The platform consists of cationized photodynamic organic nanoparticles (iTPyPXs) integrated with a silk fibroin-based nanofibrous membrane (SCM) via electrospray deposition. Cationization enhanced the local donor–acceptor (D-A) structure and electrostatic adhesion of iTPyPXs, improving visible-light-induced ROS generation at the bacteria–material interface. Meanwhile, SCM immobilized iTPyPXs and released silk fibroin to reduce excessive intracellular ROS, thereby supporting an M2-associated reparative immunomodulatory tendency. In a rat model, iTPyPXs/SCM-aPDT eradicated infection and accelerated wound closure, while promoting inflammation resolution, angiogenesis, and collagen deposition. Transcriptomic analysis further confirmed that the treatment promoted regenerative healing. Collectively, this work provides a safer and more effective biomaterial strategy for photodynamic therapy in infected wound healing.