An All-in-One Nanoplatform for Synergistic Anti-Infection and Healing of Diabetic Wounds via Photothermal-Gas Therapy

Diabetic wounds represent a significant clinical challenge, characterized by bacterial biofilm formation, persistent inflammation, and oxidative stress. Although photothermal therapy (PTT) and gas therapy (e.g., CO, H 2 ) are promising alternatives to conventional antibiotics, existing monotherapeutic strategies fail to address the multifactorial pathological characteristics of these wounds, which is a critical research gap. To fill this gap, an integrated multimodal nanoplatform (CO/AB@MPDA) by co-loading dodecacarbonyltriiron (FeCO, a CO donor) and ammonia borane (AB, a H 2 donor) into mesoporous polydopamine (MPDA) carriers was developed. The innovation lied in its synergistic design. It enabled near-infrared (NIR)-triggered CO release and pH-responsive H 2 generation, simultaneously targeting infections, inflammation, and microenvironment dysregulation. In vitro and in vivo experiments confirmed its potent antibacterial/biofilm-disrupting activity, high biosafety, reactive oxygen species (ROS) scavenging, anti-inflammatory properties, as well as superior ability to accelerate diabetic infected wound healing. In summary, the CO/AB@MPDA nanosystem overcomes the limitations of monomodal therapies through synergistic PTT-gas therapy, providing an innovative and comprehensive therapeutic strategy for diabetic wound infections.