Dual‐Modal Phototherapeutic Nanoagents Eradicating Drug‐Resistant Bacteria via Multi‐Pathway of Membrane Disruption, Oxidative Damage, and Energy Metabolism Interference

Faced with the growing challenge of antimicrobial resistance, developing non-antibiotic therapies is imperative. Photodynamic and photothermal therapy (PDT/PTT) are promising due to their minimal side effects and low risk of resistance. However, their efficacy is limited by inadequate reactive oxygen species (ROS) generation, finite photothermal conversion efficiency (PCE), bacterial antioxidant systems, biofilm barriers, and the constraints of single-modality treatments. To overcome these bottlenecks, this study innovatively co-assembled the phototherapeutic molecule Y6 with allicin (A) into the Y6A nanoplatform to achieve multi-mechanism antibacterial activity. Leveraging Y6's strong intramolecular charge transfer (ICT), extended π-conjugated backbone, and twisted long alkyl chain, Y6A simultaneously achieves efficient ROS generation and 55.2% PCE. Thus, Y6A eradicated up to 99.9% of Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (P. aeruginosa). This high efficacy is attributed to a synergistic antimicrobial strategy that couples structural disruption and oxidative damage via bimodal phototherapy with allicin-mediated suppression of biofilm formation and energy metabolism. In an MRSA-infected wound model, irradiated Y6A accelerated healing by 90%, modulating inflammation and promoting collagen deposition. This work not only confirms the exceptional PDT/PTT efficacy of Y6A against drug-resistant bacteria but also provides innovative concepts and experimental evidence for the development of synergistic phototherapeutic antibacterial materials.