面向深层活体组织的纳米发光成像分析研究

Biomedical imaging technology has important application value in the fields of early diagnosis and clinical treatment. In vivo luminescence imaging usually employs Vis-to-NIR (down-conversion) mode or NIR-to-Vis (up-conversion) mode at present. However, neither of them is suitable for imaging analysis penetrating deep living tissue. In order to meet the medical imaging diagnosis and analysis needs towards deep living tissue, this project aims to develop nano-luminescence imaging analysis technique with better penetration for living tissue, higher resolution and lower imaging noise. Herein, NIR-to-NIR nanomaterials will be fabricated to overcome the shortcoming of visible light imaging technique in biological tissue penetrating, meanwhile, increase the optical penetration depth and eliminate the background fluorescence in living tissue. Secondly, persistent luminescent nanomaterials with NIR luminescence centers will be synthesized to develop long time tracing luminescence imaging technique in deep living tissue. Moreover, a kind of novel nanomaterial will be synthesized and luminescence will be generated under low energy soft X-ray excitation. The luminescence centers could be regulated by designing the nano-matrix, in order to realize the luminescence imaging in deep tissue. This project also will construct binary collaborated assembly nanostructure to explore the new technique for in vivo imaging analysis and treatment, which is molecular targeted and signal increased under stimulation.

生物医学影像技术在疾病早期诊断和临床治疗中有着重要的应用价值。目前，活体发光成像通常采用可见光激发近红外（下转换）或近红外激发可见光（上转换）的模式，因此仍不能适用于穿透深层活体组织的影像分析。本项目旨在发展活体组织穿透能力强、分辨率高、成像噪音小的纳米发光成像分析技术，以满足深层活体组织的医学成像诊断分析的需求。将发展基于激发光和发射光均在近红外区的纳米材料，以克服可见光区成像技术在生物组织穿透性方面不足的缺点，增加光学穿透深度，消除活体组织内荧光背景；合成发光中心在近红外区的长余辉发光纳米材料，发展在深层活体组织内的长时间示踪发光成像技术；同时，我们将合成一类在低能量软X射线激发下产生发光的新型纳米材料，合理设计纳米基质并调控发光中心，实现在深层组织内的发光成像分析。本项目还将采用纳米自组装技术，构建二元协同纳米组装结构，探索在活体的分子靶向、刺激增强信号的成像分析和治疗新技术。

活体发光成像分析是疾病早期诊断和临床治疗的关键技术，在生物医学成像中有着广阔的发展前景和应用价值。针对当前纳米生物医学发光成像分析中所存在的重要挑战，本项目按照预期计划，顺利完成了以下工作：（1）研究了纳米闪烁体的X射线发光新现象与新原理，提出高效X射线发光纳米闪烁体的设计新思路，实现了深层活体组织的高灵敏高分辨的X射线发光成像分析；（2）开发了激发光和发射光均位于近红外一/二区的新型发光纳米材料，构建了肿瘤微环境等特异性响应的发光纳米探针，实现肿瘤等深层组织疾病的精准发光成像诊断；（3）制备了X射线可激活的成像纳米探针，实现了软X射线激活的深层活体组织成像与治疗；（4）发展了自组装新技术与纳米组装体新材料，实现了疾病生物标志物的高灵敏检测分析与肿瘤成像治疗研究；（5）建立了多模态生物医学影像分析新平台，实现了深层活体组织的高质量成像指引的疾病治疗。项目发展了系列具有穿透性强、灵敏度高、信噪比高、分辨率高的活体纳米发光成像分析新方法和新技术，实现了深层活体组织的精准生物医学影像分析和精准治疗。本项目研究结果发表国际高水平学术期刊论文94篇（其中Nature 2篇，Nat. Commun. 2篇，Sci. Adv. 1篇，Angew. Chem. Int. Ed. 10篇，J. Am. Chem. Soc. 4篇，Adv. Mater. 7篇，Chem. Soc. Rev. 1篇，和Anal. Chem. 9篇等），申请发明专利20项，授权发明专利5项。