De novo design of highly efficient type-I photosensitizer based on π-conjugated oligomer for photodynamic eradication of multidrug-resistant bacterial infections

Traditional photosensitizers show limited singlet oxygen generation in hypoxic infection lesions, which greatly suppress their performance in antibacterial therapy. Meanwhile, there still is lack of feasible design strategy for developing hypoxia-overcoming photosensitizers agents. Herein, radical generation of π-conjugated small molecules is efficiently manipulated by an individual selenium (Se) substituent. With this strategy, the first proof-of-concept study of a Se-anchored oligo (thienyl ethynylene) (OT-Se) with high-performance superoxide radical (O2•−) and hydroxyl radical (•OH) generation capability is present, and achieves efficient antibacterial activities towards the clinically extracted multidrug-resistant bacteria methicillin-resistant S. aureus (MRSA) and carbapenem-resistant E. coli (CREC) at sub-micromolar concentration under a low white light irradiation (30 mW/cm2). The water-dispersible OT-Se shows a good bacteria-anchoring capability, biocompatibility, and complete elimination of multidrug-resistant bacteria wound infection in vivo. This work offers a strategy to boost type-I photodynamic therapy (PDT) performance for efficient antibacterial treatments, advancing the development of antibacterial agents.