Yang Shiping, Jia Qian, Ou Xinwen, Sun Fang, Song Chaoqi, Zhao Tingxing, Kwok Ryan T K, Sun Jianwei, Zhao Zheng, Lam Jacky W Y, Wang Zhongliang, Tang Ben Zhong
Department of Chemistry, The Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Division of Life Science, State Key Laboratory of Molecular Neuroscience, and Department of Chemical & Biological Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong 999077, China.
Lab of Molecular Imaging and Translational Medicine (MITM), Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, School of Life Science and Technology, Xidian University & International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment, Xi'an, Shaanxi 710126, China.
J Am Chem Soc. 2025 Jan 29;147(4):3570-3583. doi: 10.1021/jacs.4c15216. Epub 2025 Jan 15.
The two contradictory entities in nature often follow the principle of unity of opposites, leading to optimal overall performance. Particularly, aggregation-induced emission luminogens (AIEgens) with donor-acceptor (D-A) structures exhibit tunable optical properties and versatile functionalities, offering significant potential to revolutionize cancer treatment. However, trapped by low molar absorptivity (ε) owing to the distorted configurations, the ceilings of their photon-harvesting capability and the corresponding phototheranostic performance still fall short. Therefore, a research paradigm from twisted configuration to near-planar structure featuring a high ε is urgently needed for AIEgens development. Herein, by introducing the strategy of "motion and stillness" into a highly planar A-D-A skeleton, we successfully developed a near-infrared (NIR)-II AIEgen of Y5-2BO-2BTF, which boasts an impressive ε of 1.06 × 10 M cm and a photothermal conversion efficiency (PCE) of 77.8%. The modification of steric hindrance on the benzene ring in the acceptor unit of the aggregation-caused quenching counterpart Y5-2BO, to a -CF-substituted naphthyl, leads to reversely staggered packing and various intermolecular noncovalent conformational locks in Y5-2BO-2BTF ("stillness"). Furthermore, the -CF moiety acted as a flexible motion unit with an ultralow energy barrier, significantly facilitating the photothermal process in loose Y5-2BO-2BTF aggregates ("motion"). Accordingly, Y5-2BO-2BTF nanoparticles enabled tumor eradication and pulmonary metastasis inhibition through NIR-II fluorescence-photoacoustic-photothermal imaging-navigated type I photodynamic-photothermal therapy. This work provides the first evidence that the highly planar conformation with a reversely staggered stacking arrangement could serve as a novel molecular design direction for AIEgens, shedding new light on constructing superior phototheranostic agents for bioimaging and cancer therapy.
自然界中的两个矛盾实体常常遵循对立统一的原则，从而产生最优的整体性能。特别是，具有供体-受体（D-A）结构的聚集诱导发光荧光团（AIEgens）展现出可调节的光学性质和多样的功能，为变革癌症治疗提供了巨大潜力。然而，由于构型扭曲导致摩尔吸光系数（ε）较低，它们的光子捕获能力以及相应的光热诊疗性能仍有局限。因此，对于AIEgens的发展而言，迫切需要一种从扭曲构型到具有高ε的近平面结构的研究范式。在此，通过将“动与静”策略引入高度平面化的A-D-A骨架，我们成功开发出一种近红外（NIR）-II AIEgen Y5-2BO-2BTF，其具有高达1.06×10 M cm的ε以及77.8%的光热转换效率（PCE）。将聚集导致猝灭的对应物Y5-2BO受体单元苯环上的空间位阻修饰为-CF取代的萘基，使得Y5-2BO-2BTF中形成反向交错堆积以及各种分子间非共价构象锁定（“静”）。此外，-CF部分作为具有超低能垒的柔性运动单元，显著促进了松散的Y5-2BO-2BTF聚集体中的光热过程（“动”）。相应地，Y5-2BO-2BTF纳米颗粒通过NIR-II荧光-光声-光热成像引导的I型光动力-光热疗法实现了肿瘤根除和肺转移抑制。这项工作首次证明，具有反向交错堆积排列的高度平面构象可作为AIEgens的一种新型分子设计方向，为构建用于生物成像和癌症治疗的卓越光热诊疗剂提供了新的思路。
