Light-Activated Biodegradable Covalent Organic Framework-Integrated Heterojunction for Photodynamic, Photothermal, and Gaseous Therapy of Chronic Wound Infection

Chronic wound healing, impeded by bacterial infections and drug resistance, poses a threat to global human health. Antibacterial phototherapy is an effective way to fight microbial infection without causing drug resistance. Covalent organic frameworks (COFs) are a class of highly crystalline functional porous carbon-based materials composed of light atoms (e.g., carbon, nitrogen, oxygen, and borane), showing potential applications in the biomedical field. Herein, we constructed porphyrin-based COF nanosheets (TP-Por CON) for synergizing photodynamic and photothermal therapy under red light irradiation (e.g., 635 nm). Moreover, a nitric oxide (NO) donor molecule, BNN6, was encapsulated into the pore volume of the crystalline porous framework structure to moderately release NO triggered by red light irradiation for realizing gaseous therapy. Therefore, we successfully synthesized a novel TP-Por CON@BNN6-integrated heterojunction for thoroughly killing Gram-negative bacteria Escherichia coli and Gram-positive bacteria Staphylococcus aureusin vitro. Our research identified that TP-Por CON@BNN6 has favorable biocompatibility and biodegradability, low phototoxicity, anti-inflammatory properties, and excellent mice wound healing ability in vivo. This study indicates that the TP-Por CON@BNN6-integrated heterojunction with multifunctional properties provides a potential strategy for COF-based gaseous therapy and microorganism-infected chronic wound healing.