Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Division of Life Science and State Key Laboratory of Molecular Neuroscience, and Division of Biomedical Engineering , The Hong Kong University of Science and Technology , Clear Water Bay, Kowloon , Hong Kong, China.
Department of Medical Imaging , Shanxi Medical University , Taiyuan 030001 , China.
J Am Chem Soc. 2019 Apr 3;141(13):5359-5368. doi: 10.1021/jacs.8b13889. Epub 2019 Mar 22.
Planar donor and acceptor (D-A) conjugated structures are generally believed to be the standard for architecting highly efficient photothermal theranostic agents, in order to restrict intramolecular motions in aggregates (nanoparticles). However, other channels of extra nonradiative decay may be blocked. Now this challenge is addressed by proposing an "abnormal" strategy based on molecular motion in aggregates. Molecular rotors and bulky alkyl chains are grafted to the central D-A core to lower intermolecular interaction. The enhanced molecular motion favors the formation of a dark twisted intramolecular charge transfer state, whose nonradiative decay enhances the photothermal properties. Result shows that small-molecule NIRb14 with long alkyl chains branched at the second carbon exhibits enhanced photothermal properties compared with NIRb6, with short branched chains, and much higher than NIR6, with short linear chains, and the commercial gold nanorods. Both in vitro and in vivo experiments demonstrate that NIRb14 nanoparticles can be used as nanoagents for photoacoustic imaging-guided photothermal therapy. Moreover, charge reversal poly(β-amino ester) makes NIRb14 specifically accumulate at tumor sites. This study thus provides an excited molecular motion approach toward efficient phototheranostic agents.
平面给体-受体（D-A）共轭结构通常被认为是构建高效光热治疗剂的标准，以限制聚集态（纳米颗粒）中分子的内运动。然而，其他的非辐射衰减通道可能会被阻断。为了解决这一挑战，我们提出了一种基于聚集态分子运动的“异常”策略。将分子转子和大体积的烷基链接枝到中心 D-A 核上，以降低分子间相互作用。增强的分子运动有利于形成暗扭曲的分子内电荷转移态，其非辐射衰减增强了光热性能。结果表明，与具有短支链的小分子 NIRb6 相比，具有长支链的小分子 NIRb14 具有增强的光热性能，与具有短线性链的商业金纳米棒相比，其光热性能更高。体外和体内实验均表明，NIRb14 纳米颗粒可用作光声成像引导光热治疗的纳米试剂。此外，电荷反转聚（β-氨基酯）使 NIRb14 特异性地聚集在肿瘤部位。因此，本研究为高效光热治疗剂提供了一种激发分子运动的方法。
