纳米光学效应的分子影像原理与活体分析方法

The real-time and in situ monitoring and tracking of active molecules and their biochemical processes in cells is crucial important to reveal various physiological phenomena and develop new medical diagnostic methods, the problems of which have not been solved by the traditional biological imaging technologies. Aiming to the typical molecular events occurred in cell carcinogenesis, the present research project is to develop a new principle of molecular imaging and in vivo analysis by the means of optical enhancement effect of nanostructures to light up these biochemical processes in cells (optical imaging) through the nano-optical probes for the detection and trace of the related molecular events in cells, tissues and animals. The topic will include these research aspects: (1) designing and synthesizing the novel nanoprobes with optics-enhanced effects and exploring the relationship between the nano-interface coupling and optical signal amplification; (2) synthesizing the related molecular tags and developing the new approach to its conjugation with the nanoprobes, and revealing the interaction mechanism between the nanoprobes and target molecules; (3) monitoring the active molecules and their biochemical processes by the single and multi-modal nano-optical probe, and establishing the relationship between spectral characteristics and the related molecular events; (4) the methods for imaging and tracking the biomolecules in cells, tissues and animals, and the nano-imaging reagents for the in vivo analysis. The expected results of the project will provide the theoretical foundation and technical means for the molecular imaging and its in vivo analysis.

实时原位监测和跟踪细胞内的活性物质及其生物化学过程对于揭示各种生理现象及发展新的医学诊断方法具有重要的科学意义，也是传统生物影像技术无法解决的重大科学难题。本项目针对细胞癌变过程的典型分子事件，拟发展以纳米光学效应为手段的分子影像原理和活体分析方法，通过纳米光学探针点亮细胞内生物化学过程及其影像解析，实现细胞、组织及活体内相关分子事件的检测和示踪。具体研究内容包括：（1）纳米光学探针的构建与表征，探索纳米界面耦合及探针光学信号放大机制;（2）相关分子标签构建及其与纳米探针的偶联，揭示纳米探针与目标分子相互作用机制;（3）单一和多模态纳米光学探针对活性分子及其生物化学过程的监测，建立光谱特征与相关分子事件的对应关系;（4）细胞、组织及活体内生物分子的成像与示踪，开发用于活体分析的纳米影像试剂。本项目的预期成果将为纳米分子影像学及其在活体分析中的应用提供理论基础和技术手段。

本项目针对细胞癌变过程的典型分子事件，开展了以纳米光学效应为手段的分子影像原理和活体分析方法研究。主要发现点和成果如下：（1）发展了光学性质可调的纳米材料体系，为纳米光效应探针的制备及其在分子影像分析中的应用提供了新手段；（2）针对生物活性小分子和肿瘤标志物，建立了基于纳米光效应探针的影像学检测与分析新方法，解决了细胞内自发性产生的活性物种检测与成像困难；（3）拓展了纳米光学探针在活体影像分析中的新应用，为精准医学的实现提供了可能。上述研究工作取得了多项具有创新性和系统性的研究成果，部分研究工作已经在Journal of the American Chemistry Society、Angewandte Chemie International Edition、ACS Nano、Analytical Chemistry等高影响力的国际期刊上发表SCI论文25篇。此外，还获得授权国家发明专利3项。这些研究成果为纳米分子影像学及其在活体分析中的应用提供了理论基础和技术手段。