In situ glycosylation-directed H-aggregation of Type I photosensitizers for synergistic biofilm eradication and promoting diabetic wound healing

Abstract

Biofilm-associated diabetic wound infections pose a major therapeutic challenge. Although photodynamic therapy (PDT) offers an alternative antibacterial strategy, conventional photosensitizers are often limited by inadequate biofilm penetration and poor activity under hypoxic conditions. In this study, we report glycosylated photosensitizers (NBS-Gal and NBS-Lac) that spontaneously form H-aggregates in aqueous media via π-stacking. This self-assembly integrates molecular function with nanostructure without requiring auxiliary components and enables robust Type I photodynamic activity. Notably, NBS-Lac exhibits superior H-aggregation, resulting in 2.2-fold and 1.8-fold higher O₂^˙− generation (after 4 min irradiation) than NBS-NH₂ and NBS-Gal, respectively. The glycosyl moieties enable targeted bacterial recognition through carbohydrate–lectin interactions, while the positive charge on NBS facilitates biofilm penetration via electrostatic interactions. NBS-Lac achieves 100% bactericidal efficacy against P. aeruginosa, along with high biofilm inhibition (∼87%) and eradication (∼80%). In a murine diabetic wound model, NBS-Lac mediates complete healing (100%) under light irradiation, significantly outperforming the controls. This work establishes carbohydrate-directed self-assembly as a novel paradigm for designing targeted, hypoxia-tolerant Type I PDT agents.