Aggregation‐Induced NIR‐II Emission Luminogens Integrated into Cu 2+ ‐Phenolic Nanoparticles for Mild‐Temperature Photothermal Eradication of Bacterial Biofilms

ABSTRACT Drug‐resistant biofilm infections pose a critical global health challenge, demanding innovative therapies. We developed a butterfly‐shaped aggregation‐induced emission luminogen (AIEgen), 4TPE‐DTB, as a potent photothermal agent for biofilm eradication. Encapsulating 4TPE‐DTB into pH‐responsive Cu 2 + ‐tannic acid nanoparticles (CTNPs) yielded a synergistic platform (DTB@CTNPs) combining mild photothermal therapy (PTT) with controlled Cu 2 + release. DTB@CTNPs exhibited strong bacterial membrane adhesion and acid‐triggered Cu 2 + release, specifically targeting biofilm microenvironments. 4TPE‐DTB enabled NIR‐II imaging‐guided therapy, permitting real‐time infection localization while generating localized hyperthermia under 808 nm irradiation. The photothermal effect disrupted bacterial membranes, enhancing intracellular Cu 2 + influx and antibacterial efficacy. In vitro, DTB@CTNPs eradicated mature biofilms at low doses. In vivo, they effectively treated methicillin‐resistant Staphylococcus aureus (MRSA) abscesses and Pseudomonas aeruginosa keratitis, demonstrating superior antibiofilm performance. This work presents a multifunctional nanoplatform synergizing AIEgen‐mediated mild PTT and Cu 2 + delivery, achieving potent bactericidal activity with minimal cytotoxicity. The strategy addresses a pressing unmet need in combating drug‐resistant biofilm infections.