Hypoxia-Activated Biodegradable Porphyrin-Based Covalent Organic Frameworks for Photodynamic and Photothermal Therapy of Wound Infection

Wound infections have gradually become a major threat to human health. Recently, covalent organic frameworks (COFs) have shown great potential in antibacterial and wound healing; however, difficult biodegradability and long-time in vivo retention limit their further application. Herein, biodegradable COFs containing porphyrin backbones and hypoxia-sensitive azobenzene group, namely, HRCOFs, are fabricated for photodynamic therapy (PDT) and photothermal therapy (PTT) of wound infection. Due to the introduction of a porphyrin molecule, HRCOFs can produce singlet oxygen (¹O₂) under 660 nm laser irradiation. The prepared HRCOFs can also generate thermal energy under 808 nm NIR laser irradiation. HRCOFs show excellent synergetic antibacterial ability against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) in vitro. The in vivo experiments also demonstrate synergistic PDT and PTT effects of HRCOFs against wound infection. Importantly, HRCOFs are response to wound microenvironment, can be degraded for clearance, and avoid some adverse effects caused by long-time retention in vivo, exhibiting good biocompatibility. In general, the obtained biodegradable HRCOFs with both photodynamic and photothermal effects can be used for antibacterial infections and provide great value for promoting wound healing.