高质量近红外荧光金纳米簇的制备及其在生物成像中的应用研究

Fluorescence imaging provides an important analytical tool for many research areas such as molecular biology and medicine, for which the development of robust near-infrared fluorescence probes has been the key determinant. Gold nanoclusters are one type of novel fluorescence nanoprobes developed in recent years. Because of their ultrasmall size, good chemical stability as well as excellent biocompatibility, gold nanoclusters are considered as one of the most promising nanoprobes for biological imaging. However, currently most reported gold nanoclusters exhibit poor colloidal stability in biological environment and low fluorescence quantum yield in the near-infrared region, which greatly restrict their further biological application. Therefore, the present project aims to develop high quality near-infrared fluorescent gold nanoclusters by systematically screening the surface ligands in combination with detailed characterization of their physicochemical properties, upon which a clear understanding toward the structure-property relationship of metal nanoclusters can be obtained. Investigation on the behavior of gold nanoclusters in biological systems will also be performed by using molecular spectroscopy and microscopy techniques, in order to further evaluate their potential utility for biological imaging. Results from this project are expected to deep our understanding of the optical property of metal-based nanoprobes and further advance biological application of fluorescent gold nanoclusters.

荧光成像技术是当前生物分析、医学等领域的一个重要的研究工具，发展高质量的近红外荧光探针一直是荧光成像技术发展中的热点和难点之一。金纳米簇是近些年来基于纳米科技发展的一类新型荧光探针，具有尺寸超小、化学稳定性好、生物相容性优异等特点，被认为是在生物成像研究中最具有应用前景的材料之一。然而，目前已报道的金纳米簇普遍存在分散稳定性差、发光效率低等问题，极大地制约了金纳米簇在生物成像中的实际应用。本项目拟从阐明纳米材料的结构-性能关系的角度入手，通过系统的配体调控和深入的性能表征探索金纳米簇的表面配体与其发光性质的关系，以期从理论上指导高质量近红外荧光金纳米簇的制备。通过分子谱学和荧光成像等技术原位评估金纳米簇和生物体系的相互作用，为该类材料的生物应用提供实验支撑，进而开发基于高质量的荧光金纳米簇的生物学应用。本项目有望加深对金属纳米材料的光学性能的认识，推动荧光金纳米簇在生物成像等领域的应用。

金纳米团簇由于具有尺寸超小、化学稳定性好、生物相容性优异等特性，被认为是在生物成像研究中极具应用前景的新型荧光纳米探针。然而，目前已报道的荧光金纳米团簇普遍存在分散稳定性差、近红外发光效率低等问题，极大地制约了金纳米团簇在生物成像中的实际应用。本项目针对此问题，围绕高性能近红外荧光金纳米团簇的设计合成、构效关系及成像性能开展了相关的研究，主要取得的创新工作和成果包括：. （1）通过对表面配体的工程化设计与系统调控，开发了系列发光效率高、稳定性好的近红外荧光金纳米团簇，通过各种微纳米结构表征技术和分子谱学方法研究了所制备的金纳米团簇的结构和光学性能，其中荧光发射峰的位置可调控至830 nm，荧光量子产率最高可达到30%。. （2）结合表面配体的化学调控与光学性能的机理分析，探究了金纳米团簇的近红外发光性能与其结构之间的关系，在此基础上通过采用精确调控生物模板的表面电荷、多孔材料组装体的限域效应等策略成功实现了金纳米团簇近红外发光性能的显著提升。. （3）通过对金纳米团簇与常见血清蛋白质相互作用的机理研究，揭示了生物环境下影响金纳米团簇性能的关键因素，在此基础上研究了金纳米团簇在细胞成像和胞内药物递送等方面的应用性能，为推动金属纳米团簇的生物应用提供了新的研究思路。. 通过上述创新工作本项目取得了较好的科研成果：三年间已发表8篇研究论文，包括Nano Today、Small、Chem. Commun.等，申请了3项国家发明专利；受邀在国内外学术会议做邀请报告6次，撰写英文专著1章。