Photoresponsive nitric oxide photocage/photodynamic integrated prodrug for advanced management of drug-resistant bacteria-infected wound therapy.

Single treatment methods for wound infections caused by drug-resistant bacteria often fail to simultaneously achieve high antimicrobial efficacy and wound healing efficiency. Therefore, it is crucial to develop a small molecule prodrug that can achieve both goals, in this context, we have engineered a green-light-activated nitric oxide photocage/photodynamic therapeutic prodrug, designed to release NO, which not only potentiates antimicrobial efficacy but also facilitates collagen accumulation at the wound interface, thereby expediting the wound healing process. Additionally, it mitigates tissue inflammation by suppressing the NF-κB signaling pathway. In addition, the introduction of the photosensitiser rhodamine can be used for antimicrobial photodynamic therapy (aPDT) against Methicillin-resistant Staphylococcus aureus (MRSA). aPDT exhibits enhanced antimicrobial efficacy by specifically targeting and disrupting bacterial cell membranes. Notably, this treatment significantly reduced bacterial viability in vitro and accelerated healing of MRSA-induced wound infections even at low concentrations. The developed NO photocage/photodynamic prodrug RhB-NO-1 is biocompatible and has demonstrated the ability to significantly accelerate the healing process of diabetic foot ulcers (DFU), making it a promising next-generation pharmacological treatment for chronic wound management.