Aggregation-induced BODIPY photosensitizers for synergistic type I/II photodynamic antibacterial therapy.

Abstract

This study designed two heavy-atom-free boron dipyrromethene (BODIPY) photosensitizers with aggregation-induced emission (AIE) to overcome the aggregation-caused quenching (ACQ) and alleviate heavy-atom toxicity, aiming to enhance the antimicrobial photodynamic therapy (aPDT) of conventional BODIPY. The resulting photosensitizers, TPA-BDP and TPE-BDP, were efficiently synthesized via a one-pot strategy by incorporating triphenylamine or tetraphenylethylene electron donors at the meso-position of the BODIPY core. Upon 525 nm light irradiation, these compounds generate substantial reactive oxygen species (ROS) in the aggregated state without requiring heavy atom substitution. The ROS produced by TPA-BDP and TPE-BDP were identified as singlet oxygen (1O2) and superoxide anion (O2•-), enabling combined Type I/Type II photodynamic mechanisms that improved antibacterial activity. Antibacterial activity was evaluated against Gram-positive Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA) under irradiation using the plate counting method, with both photosensitizers exhibiting minimum inhibitory concentration below 6 μM. In vivo anti-MRSA efficacy, topical application of these photosensitizers followed by irradiation significantly accelerated wound healing while maintaining excellent biosafety, with the wound healing rate reaching over 90%. Collectively, these heavy-atom-free BODIPY photosensitizers integrate AIE, Type I/II aPDT activity, and in vivo wound-healing performance against MRSA, thus successfully addressing the major limitations of conventional BODIPY photosensitizers.