Yu Yanlu, Wang Yanfen, Wu Baixuan, Yu Qiqi, Ye Jingtao, Chen Yaofeng, Qian Jun, Li Yang, Yin Shouchun
Key Laboratory of Organosilicon Chemistry and Materials Technology of the Ministry of Education, Zhejiang Key Laboratory of Organosilicon Material Technology, College of Materials, Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou, Zhejiang Province, 311121, P. R. China.
State Key Laboratory of Modern Optical Instrumentations, Centre for Optical and Electromagnetic Research, College of Optical Science and Engineering, International Research Center for Advanced Photonics, Zhejiang University, Hangzhou, 310058, P. R. China.
Small. 2025 Sep;21(35):e2504607. doi: 10.1002/smll.202504607. Epub 2025 Jul 4.
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 = 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 ), BTA-BDP nanoparticles (NPs) induce rapid hyperthermia (ΔT = 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.
在单一纳米平台中将高性能近红外二区（NIR-II，900-1880纳米）荧光成像与高效光热疗法（PTT）相结合，在癌症诊疗中仍然是一项艰巨的挑战。在此，我们提出了一种利用硼-氧（B-O）螯合的超分子工程策略，以构建构象锁定的氮杂硼二吡咯衍生物（BTA-BDP），其可自组装成超稳定的J-聚集体。这一设计实现了双重突破：1）在近红外二区窗口（λ = 1014纳米）中荧光量子产率（Φ）为4.37%，超过了近红外二区发射体典型的Φ < 1%的障碍；2）创纪录的光热转换效率（PCE）为69.6%，超过了大多数有机光热剂（PCE < 50%）。分子动力学模拟和药代动力学研究表明，强π-π堆积相互作用和长烷基链的结合延长了肿瘤滞留时间（>344小时），使得能够单剂量给药。在低功率808纳米照射（0.4 W cm）下，BTA-BDP纳米颗粒（NPs）在小鼠模型中诱导快速热疗（ΔT = 25.9°C）并实现完全肿瘤消融，经组织病理学和多模态成像（近红外二区/光声）验证。这项工作解决了荧光-光热权衡问题，并建立了精确癌症纳米医学的超分子蓝图，从而弥合了分子工程与临床转化之间的差距。
