基于近红外二区染料的轮烷体系构建及其活体荧光成像研究

Due to the advantage of non-invasion, visualization, low cost, safety and fast speed, the fluorescence imaging have been widely applied to chemistry, biology and medical science, and near-infrared window imaging is at the forefront of the research on optical imaging techniques. The near-infrared fluorescence can be classified to the first near-infrared window (NIR-I) and the second near-infrared window (NIR-II) according to the wavelength. Compare with NIR-I, the NIR-II region have several advantages: deeper tissue imaging, high spatial resolution, and high contrast owing to minimal auto-fluorescence and tissue scattering. However, NIR-II dyes suffer from low quantum yield, self-aggregation, photobleaching and instability, which significantly restricted their applications. In this project, we would like to synthesize a macrocycle which can complex the NIR-II dye, leading to a dye rotaxane for fluorescence imaging. The dye was locked in the hydrophobic cavity of the macrocycle, which may result in a higher quantum yield, chemical stability and prevent from self-aggregation. We will study the property of the dye rotaxane and apply for fluorescence imaging in vivo. We will attach the dye rotaxane with RGD peptide, and further realize the targeted tissue fluorescence imaging. This research would enhance the applicability of NIR-II dye in vivo.

荧光成像因其非侵入、可视化、成本低、安全和快速等优势已广泛应用于化学、生物及医学等领域，而近红外荧光成像则是光学成像的最前沿研究工作。近红外光根据其波长可以分为近红外一区（NIR-I）和近红外二区（NIR-II）。相比于近红外一区，近红外二区的光具有更深的穿透深度，更好的成像效果等。然而，常规的近红外二区染料荧光量子产率低，且易自聚集、光漂白、化学不稳定等缺陷限制了其应用。本项目拟通过设计合成与近红外二区染料相匹配的新型超分子大环主体，构建内锁型的染料轮烷体系，将近红外二区染料牢牢的锁在大环主体的疏水空腔中，从而提高染料的荧光量子产率，化学稳定性，防止自聚集。研究轮烷的性质并应用于活体荧光成像。在染料轮烷上修饰靶向多肽RGD，进一步实现肿瘤组织的靶向荧光成像。本项目的研究将提高近红外二区染料在生物体中的适用性。

分子识别是超分子化学的基础，大环主体则是超分子化学的重要工具。基于超分子大环主体独特的分子识别性能构建新型的分析检测平台受到了越来越多的关注。本项目在三年的执行期间，设计并合成了多种仿生大环主体，研究了这类仿生大环主体的主客体识别性质，并成功将其应用于有机小分子化合物、药物及天然产物的手性传感，污染物的识别检测和贵金属的捕获回收利用。同时，在大环主体的合成过程中，发现了一种新的聚集诱导发光（AIE）分子骨架，并提出了孤电子•••π的AIE新机理。这些研究结果对丰富大环主体类型，发展基于超分子大环主体的分析测试平台都具有重要的科学意义。