Sunlight triggered radical oxygen species redistribution in infected wound treatment.

Abstract

Photodynamic therapy achieves antibacterial effects by generating reactive oxygen species (ROS), and is therefore used in the clinical treatment of infectious wounds. However, generated ROS also causes damage to surrounding normal tissues and exacerbates the inflammatory response inevitably, which restrict the application scope of PDT. To address this problem, we developed a new photosensitizer, l-arginine(L-Arg) modified zinc oxide (ZnO) nanoparticles (AL-ZnO NPs). Under sunlight illumination, the high-dose oxygen (·O₂^-) and hydroxyl radicals (·OH) generated by ZnO were converted to low-dose yet highly reactive peroxynitrite (ONOO^-) through the L-Arg mediated cascade reaction, which preserved antibacterial activity of produced ROS while preventing the adverse effects of excessive ROS leakage on surrounding tissues. Concurrently, sustained Zn²⁺ releasing from AL-ZnO NPs activated intracellular superoxide dismutase (SOD) associated antioxidant pathway to counteract ROS-induced negative effect to normal cells, while promoting macrophage polarization from M1 to M2 to reduce inflammation. Then, the well-designed AL-ZnO NPs were encapsulated freeze-thaw polyvinyl alcohol (PVA) hydrogel to prepare composite hydrogel dressing. Our in vitro and in vivo evaluations confirmed that this hydrogel addressed the challenge caused by excessive ROS in PDT, achieved potent antibacterial efficacy, protected normal tissue from ROS damaging, reduced inflammation, and finally promoted the healing of infected wounds.