荧光/核磁共振/拉曼多模态成像碳点的构建及应用研究

Carbon dots (Cdots), as a new kind of probes, have been used for fluorescence imaging. The development of the other imaging modalities of Cdots is interesting and critical because of their low toxicity and high biocompatibility. This project aims at the development of multi-modal-imaging probes using Cdots including fluorescence, Raman, and nuclear magnetic resonance imagings (MRI), and the study of the formation mechanism of Cdots using isotope C-13. The formation mechanism and structure of Cdots will be studied using the nuclear magnetic resonance signals of H-1 and C-13. The Cdots with enriched C-13 will be prepared as fluorescence-MRI dual-modal imaging probes. C-13 and C-12 show different Raman shift and the C dots with different ratios of C-13/C-12 will be used for the multi-color Raman-MRI dual-modal imaging. Cdots-gold nanoparticle composite will be prepared and used as Raman imaging-phototherapy probes with the surface enhanced Raman and photo-thermal properties of gold nanoparticles. The project will provide the extended knowledge about Cdots' formation and optical mechanism and broaden the applications of Cdots in the field of multi-modal imaging. Different to the multi-modal probes combining different imaging units, the present multi-modal Cdots can be prepared one-step because C-13 has Raman and magnetic resonance responses and is the component of fluorescence Cdots.

碳点作为一种新型探针，已有荧光成像的报道，充分利用其低毒性和高生物相容性，开发碳点的其他成像模式具有重要意义。本项目首次将同位素C-13引入碳点，利用C-13的核磁共振和拉曼信号，构建基于碳点的荧光-拉曼-核磁共振多模态成像探针。通过碳点制备过程中H-1和C-13核磁共振信号的变化研究碳点的结构和形成机理；合成富C-13碳点作为荧光-核磁共振双模态成像探针；C-13和C-12具有不同拉曼位移，调控碳点中C-13/C-12比例，利用拉曼位移的不同实现碳点的多色拉曼-核磁共振双成像；制备碳点-纳米金复合材料，利用纳米金的增强拉曼和光热效应，构建拉曼成像-光疗探针。本项目的实施将加深对碳点形成和发光机理的认识，拓宽碳点在多模态成像中的应用。与将不同功能单元组合的多模态成像探针不同，C-13既拥有核磁共振和拉曼信号，又是荧光碳点的组成部分，实现一步合成同时集成多种成像模式。

碳点是一种新型的纳米荧光材料，具有制备成本低，生物相容性好等优点。发展新颖的碳点制备方法，研究其发光机理，拓展其应用对于推动碳点及相关领域发展具有重要意义。在项目资助下，我们提出了碳化-溶剂萃取制备高发光效率碳点新方法，实现了简单的中和反应热法快速制备碳点，发展了制备碳点的溶剂热法。结合不同碳点的发光特性，提出了碳点的发光机理：碳点的π-交联内核作为量子限域中心吸收光子，经表面弛豫发出荧光，激发依赖发光特性是由碳点的不均质性造成的。充分利用碳点生物相容性好的特点，拓展为荧光-磁共振双响应探针：一步制备了13C-碳点并研究了其荧光和磁共振性质；制备了碳点保护的钆离子复合探针以及红光发射碳点-钆复合探针，成功实现了碳点荧光-磁共振双模态成像。以细胞、斑马鱼和小鼠为模型验证了所制备碳点的应用。相关成果发表SCI收录论文20篇，获授权中国发明专利和分析测试协会科学技术二等奖各一项。