Boron–Oxygen Chelation‐Enabled Aza‐BODIPY J ‐Aggregates: NIR‐II Imaging and Photothermal Therapy for Single‐Dose Tumor Ablation

Abstract Integrating high‐performance near‐infrared‐II (NIR‐II, 900–1880 nm) fluorescence imaging with efficient photothermal therapy (PTT) in a single nanoplatform remains a formidable challenge in cancer theranostics. Herein, a supramolecular engineering strategy leveraging boron–oxygen (B–O) chelation is presented to construct conformationally locked aza‐BODIPY derivatives (BTA‐BDP) that self‐assemble into ultrastable J ‐aggregates. This design achieves dual breakthroughs: 1) a fluorescence quantum yield ( Φ ) of 4.37% in the NIR‐II window ( λ em = 1014 nm), surpassing the typical Φ < 1% barrier for NIR‐II emitters; and 2) a record photothermal conversion efficiency (PCE) of 69.6%, exceeding most organic photothermal agents (PCE < 50%). Molecular dynamics simulations and pharmacokinetic studies reveal that the combination of strong π–π stacking interactions and long alkyl chains prolongs tumor retention (>344 h), enabling single‐dose administration. Under low‐power 808 nm irradiation (0.4 W cm − 2 ), BTA‐BDP nanoparticles (NPs) induce rapid hyperthermia (Δ T = 25.9 °C) and complete tumor ablation in murine models, validated by histopathology and multimodal imaging (NIR‐II/photoacoustic). This work resolves the fluorescence‐photothermal trade‐off and establishes a supramolecular blueprint for precision cancer nanomedicine, thereby bridging the gap between molecular engineering and clinical translation.