Stiffness-Tunable Phenolic Nanocapsules Loaded with J-Aggregates for Near-Infrared II Imaging-Guided Phototherapy of Bacterial Infections.

Near-infrared II (NIR-II) imaging-guided photothermal therapy (PTT) represents a promising noninvasive strategy for treating bacterial infections. However, its efficacy is often limited by poor agent accumulation at infection sites and insufficient penetration into biofilms. Herein, we developed stiffness-tunable phenolic nanocapsules (NCs) loaded with NIR-II J-aggregates for enhanced biofilm phototherapy. Specifically, the NIR-II photothermal molecule of BTPTIC was synthesized and assembled with 8-arm-PEG-OH to form J-aggregates (BTPTIC@PEG J-aggregates). The BTPTIC@PEG J-aggregates were used as mineralizers to synthesize zeolitic imidazolate framework-8 (ZIF-8), followed by template etching with tannic acid (TA) to obtain J-aggregate-loaded phenolic NCs (BTPTIC@PEG-TA NCs). The resulting NCs not only display strong NIR-II fluorescence and a high photothermal conversion efficiency up to 82.1% but also exhibit tunable stiffness by varying TA concentration. Notably, we demonstrate that softer NCs achieve superior accumulation in infected tissues and deeper penetration into bacterial biofilms, leading to a significantly enhanced antibacterial performance. Furthermore, the NCs exhibit pH-responsive degradation within acidic infection microenvironments, releasing TA with potent anti-inflammatory activity. This synergistic integration of NIR-II imaging-guided high-efficiency PTT and inflammation modulation enables the effective treatment of both superficial (e.g., wounds) and deep-tissue (e.g., pneumonia) bacterial infections. This work highlights carrier stiffness as a crucial design parameter for developing advanced antimicrobial nanotherapeutics.