A novel ROS switcher potentiates the type-I photodynamic effect of sodium zinc chlorophyllin against Pseudomonas aeruginosa in diabetic wounds.

Skin wound infections present a serious threat to human health, with bacterial infections in diabetic wounds being particularly challenging due to impaired healing. Gram-negative bacteria are common pathogens in diabetic wound infections and often exhibit high resistance to conventional treatments, necessitating prolonged and costly therapies. Photodynamic antibacterial therapy (PACT) is regarded as a non-invasive and effective approach, with minimal risk of inducing resistance. Sodium zinc chlorophyllin (ZnChl), a water-soluble metalloporphyrin photosensitizer, offers multiple advantages such as low cost, high safety, and the ability to promote wound healing. However, its bactericidal efficacy against Gram-negative bacteria is limited under the hypoxic conditions typically found in diabetic wounds. Herein, we report a strategy to develop an efficient chlorophyll-based photosensitizer operating via an oxygen-independent Type I mechanism by combining ZnChl with inorganic salts (NaI, KBr, or KI). This approach significantly improved antibacterial performance, particularly with NaI or KI. Upon 630 nm light irradiation, low concentrations of KI (5 mM) markedly enhanced the bactericidal effect of ZnChl (50 μM), reducing the survival of three Gram-negative bacterial strains by 3 logs (99.9%). Interestingly, we further discovered that KI acts as a "reactive oxygen species (ROS) converter," shifting the photodynamic mechanism of ZnChl from a mixed Type I/Type II mode to a dominant Type I mechanism, generating highly reactive hydroxyl radicals (OH). Moreover, the ZnChl-KI combination demonstrated significant therapeutic efficacy in treating Pseudomonas aeruginosa-infected diabetic wounds without inducing apparent toxicity in rats. This work provides a foundation for developing efficient and economical Type I photosensitizers for the treatment of bacterial infections in diabetic wounds.