Boron–Oxygen Chelation‐Enabled Aza‐BODIPY <i>J</i> ‐Aggregates: NIR‐II Imaging and Photothermal Therapy for Single‐Dose Tumor Ablation
Yanlu Yu, Yanfen Wang, Bolin Wu, Qiqi Yu, Jingtao Ye, Yaofeng Chen, Jun Qian, Yang Li, Shouchun Yin
Abstract
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.