The development of antibiotic-resistant bacteria represents a major obstacle to the effective and timely management of bacterial infections, including acute bacterial skin and skin-structure infections (ABSSSI), particularly when biofilms are present. Bacterial biofilms exhibit inherent resistance to antibiotics and the host immune response, rendering biofilm-associated infections exceptionally challenging to eradicate. Consequently, the creation of novel antibacterial strategies that specifically target biofilms is of critical importance. Aggregation-induced emission luminogens exhibiting fluorescence in the second near-infrared window (NIR-II AIEgens), which can be activated by near-infrared laser irradiation to produce heat, provide a highly effective and targeted approach for photothermal therapy (PTT) in the treatment of deep-tissue bacterial infections. Nevertheless, biofilms hinder the penetration of photosensitizers into the infected site, often necessitating elevated drug concentrations and thereby increasing the potential risks associated with PTT. In this work, we engineered a biocompatible AIEgen-based biohybrid nanoformulation that integrates the NIR-II AIEgen BPBBT with antibiofilm α-amylase within a nanovesicle carrier derived from red blood cell (RBC) membranes, enabling a combined PTT and biofilm degradation strategy. The synergistic interaction of this formulation markedly improves both the photothermal performance of BPBBT and biofilm disruption relative to conventional monotherapies. This innovative combination therapy exhibited substantial efficacy in addressing severe Staphylococcus aureus biofilm-mediated infections both in vitro and in vivo, offering a promising alternative to conventional antibiotic treatments.
