Synergistic Eradication of Bacterial Biofilms via Phage‐Driven EPS Disruption and Click‐Activated AIE Photosensitization

Biofilm-associated infections pose a major clinical challenge due to their robust resistance to conventional antimicrobial treatments, primarily driven by the protective extracellular polymeric substances (EPSs) that shield bacteria. Existing strategies struggle to eliminate mature biofilms effectively. In response, a novel therapeutic approach is developed, which integrates phage T4 with a clickable aggregation-induced emission photosensitizer, pyone-TPE-BT. This approach leverages the unique properties of phage T4, including its polysaccharide depolymerase activity and bacterial infectivity, to degrade EPSs and lyse bacterial cells, thereby dismantling the biofilm structure. The disruption facilitates deeper penetration of pyone-TPE-BT, which forms covalent bonds with biofilm components via non-specific click bioconjugation. This process minimizes the distance between reactive oxygen species and their targets, leading to a significant increase in antibacterial efficacy. The strategy achieves remarkable bacterial eradication against both immature and highly mature biofilms, including host and non-host bacteria. In vivo studies demonstrate that this combined therapy not only eradicates biofilm infections but also accelerates wound healing by modulating the inflammatory microenvironments. This work establishes a promising platform for treating biofilm-related infections, holding great potential for overcoming antimicrobial resistance.