高效近红外二区发光稀土纳米探针及其肿瘤分子成像研究

Second window near-infrared (NIR-II) fluorescence imaging has aroused great attentions in various fields including deep-tissue bioimaging due to the low tissue background and improved light penetration. In this project, we aim to develop highly NIR-II luminescent lanthanide nanoprobes and demonstrate the application for tumor molecule imaging. To break through the NIR-II luminescence efficiency, the controllable synthesis of Nd3+/Yb3+/Er3+ co-doped NaLuF4 nanoparticles (NPs) will be demonstrated. And the factors that influence the NIR-II luminescence efficiency will be investigated, including host materials, core-shell structure, ion doping and surface structure. The approaches to make highly biocompatible lanthanide nanoprobes will be investigated. NIR-II fluorescence bioimaging targeting to tumor cell and tumor vasculature will be demonstrated. Besides, smart assemblies with NIR-II fluorescence resonance energy transfer will be constructed, allowing for acid pH- and tumor microRNA-responsive turn-on NIR-II fluorescence imaging. Prospectively, highly NIR-II luminescent lanthanide NPs would be obtained with quantum yields of 40% in oil phase and 10% in aqueous phase respectively. Tumor-specific NIR-II fluorescence imaging will be achieved by utilizing multiple tumor targeting and tumor environment responsive turn-on NIR-II fluorescence imaging. Therefore, the research in this project would play important roles in the fields of bioscience and clinical diagnosis.

近红外二区荧光成像因其具备荧光背景低和穿透深度高等特性，在深层活体组织成像等应用中备受关注。本项目致力于研发高效近红外二区发光稀土纳米探针并实现其在肿瘤分子成像中的示范应用；开展Nd3+/Yb3+/Er3+掺杂NaLuF4纳米晶的控制合成，揭示近红外二区发光效率与材料基质、核壳结构、离子掺杂、表面结构等的关系，突破稀土近红外二区荧光量子产率瓶颈；研发生物相容性近红外二区发光稀土纳米探针，实现肿瘤细胞和肿瘤血管等多重靶向的近红外二区荧光成像；构建基于近红外二区荧光共振能量传递的智能组装体，实现微酸性环境和肿瘤microRNA等刺激响应的“开关”型近红外二区荧光成像。预期本项目研制的油相和水相稀土纳米晶的近红外二区荧光量子产率分别突破40%和10%，通过肿瘤多重靶向成像和肿瘤环境刺激响应的“开关”型近红外二区荧光成像，实现肿瘤特异性近红外二区荧光成像，在生命科学和临床诊断等领域将发挥重要作用。

稀土发光纳米探针已成为疾病早期诊断和分子成像等生物应用研究中的一种重要工具。针对当前近红外一/二区发光稀土纳米探针及其体外诊断与活体成像研究中所面临的关键难题，本项目按照预期计划，顺利完成了以下工作：（1）研究了稀土发光纳米探针的设计新策略，发展了针对体外复杂生物样品的荧光谱学分析新方法，实现了血样疾病生物标志物的无背景高灵敏荧光检测分析；（2）构建了新型近红外二区发光稀土纳米探针，实现了活体深层组织的高分辨荧光成像和精准分子成像分析；（3）开发了基于金纳米团簇和量子点的近红外二区荧光成像新技术，实现了细胞和活体水平的高效肿瘤成像分析。本项目共发表高水平学术论文13篇，包括Angew. Chem. Int. Ed. 3篇，Adv. Funct. Mater. 2篇，Nano Today 1篇，Sci. China Mater. 1篇和Anal. Chem. 1篇等，申请发明专利3项。