An activatable type I photosensitizer for NIR fluorescence imaging and photodynamic therapy of drug-resistant bacterial infections

Bacterial infections pose a significant global health challenge, further exacerbated by the emergence of antibiotic-resistant strains, thereby necessitating the development of alternative therapeutic strategies. Type I photosensitizers, as an emerging phototheranostic modality, hold great promise for antibacterial treatment but are limited by poor specificity. Herein, we report a hydrogen sulfide (H 2 S)-activatable theranostic probe (CyIN) that integrates near-infrared (NIR) fluorescence imaging and type I photodynamic therapy (PDT) functionalities into a single platform for the precise treatment of drug-resistant bacterial infections. CyIN is rationally constructed by masking the hydroxyl group of iodine-substituted hemicyanine with a H 2 S-cleavable 2,4-dinitrophenyl group, which efficiently quenches NIR fluorescence and suppresses reactive oxygen species generation. Such molecular configuration allows CyIN to turn on its NIR fluorescence signal and type I photodynamic action upon interaction with bacterial-derived H 2 S, achieving distinguishable detection of drug-resistant bacterial infection, potent bacterial clearance (>99 %), and accelerated healing of bacteria-infected wounds. Furthermore, histological analyses confirm that the CyIN treatment can reduce inflammation, enhance collagen deposition, and promote tissue regeneration without systemic toxicity. Thus, this work presents a promising H 2 S-responsive phototheranostic platform for precise bacterial detection and efficient photodynamic eradication of drug-resistant bacterial infections.