基于聚集诱导发光特性的肿瘤探针的合成及构效关系研究

Malignant tumor (cancer) is not only one of the major diseases that threaten human health, but also the leading cause of death worldwide. Early prevention and screening is an effective way to reduce cancer mortality. Developing simple and convenient, low cost and highly reliable techniques for early diagnosis of tumor thus has extremely important practical significance. In view of the multitudinous advantages of fluorescence techniques, in this project, we propose to creatively develop novel and high-performance fluorometric probes for tumor detection by making full use of the aggregation-induced emission (AIE) characteristics. We will design and synthesize AIE probes which are capable of specifically recognizing tumor/cancer. Meanwhile, the practicability of the AIE probes for real-sample analysis or clinical diagnosis of tumor will be assessed in a comprehensive way from the molecular, cellular and tissue levels. Red/near-infrared light-emitting and water-soluble AIE tumor probes will be constructed in pursuit of clinically usable AIE systems that can accurately diagnose early-stage tumors. Compared with the existing clinical diagnosis tools, the advantages of AIE-based tumor probes include nontoxicity, low damage, superb sensitivity, high signal-to-noise ratio, low cost, and being able to visualize focus and provide real-time guidance for operations, etc. This project will also systematically study the relationship between the molecular structures of AIE probes and their tumor detection performance, with the aim to shed light on the design of new AIE-based efficient tumor probes, offer new insights into this global research hot topic and open new avenues for early diagnosis, prevention and treatment of tumor.

恶性肿瘤是目前威胁人类健康的主要疾病之一，同时也是全球首要死因。早期预防与筛查是降低肿瘤死亡率的有效途径。发展简单方便、费用低且可靠性高的肿瘤早期诊断方法具有极其重要的现实意义。鉴于荧光技术的诸多优点，本项目拟利用聚集诱导发光（AIE）特性创新地发展可用于肿瘤检测的新型荧光探针。拟设计合成能特异性识别肿瘤的AIE探针，从分子水平、细胞水平以及组织水平来综合评估AIE探针在实际肿瘤样品检测或临床诊断中的实用性；发展红光/近红外发光以及水溶性的AIE肿瘤探针，得到可准确诊断早期肿瘤且具有临床实用价值的AIE体系。与现有的临床诊断手段相比，AIE肿瘤探针的优势在于低毒、无损害、高灵敏度、高信噪比、低成本以及能可视化指导手术等。本项目还将系统地研究AIE探针的分子结构与其肿瘤检测性能之间的相互关系，旨在凝练AIE肿瘤探针的设计原则，为这一国际研究热点提供新见解，为肿瘤的早期诊断与防治开辟新途径。

荧光探针具有检测灵敏度高、选择性好、响应快、低背景噪音、操作简便、价格低廉等诸多优点。荧光手段已成为现今生命科学以及分析化学等领域最重要的技术手段之一，开发新型的荧光探针具有重要意义。荧光探针的性能极大地依赖于荧光材料的性能，研发新的高性能的荧光材料是发展荧光探针的基础和重要保障。聚集诱导发光（AIE）材料和振动诱导发光（VIE）材料是目前最具优势的两类荧光材料。鉴于此，本项目针对新型荧光探针体系的开发，聚焦聚集诱导发光和振动诱导发光，构建结构简单且性能优良的荧光探针并系统研究了其构效关系。通过本项目的实施，我们取得如下研究进展：（1）基于聚集诱导发红光的荧光探针的构筑、构效关系研究及其在巯基氨基酸和硫醇化合物的区别性便捷检测中的应用；（2）基于振动诱导发光和聚集诱导发光协同作用的新型荧光探针的构建及其在汞离子、银离子以及粘度检测中的应用；（3）基于振动诱导发光效应的二氢二苯并吩嗪类超敏温度探针的构筑及其构效关系研究；（4）基于振动诱导发光的原位实时监控特定过程如凝胶化过程以及聚合物微相分离过程的比率型探针的构筑及构效关系研究。本项目通过实验与理论相结合，为拓展新型发光材料在荧光探针领域的应用提供了新思路，丰富了高性能荧光探针的种类及分子设计方法。在基金的支持下，以第一作者身份或通讯作者身份在国际知名或权威学术期刊上发表标注受本项目资助的SCI论文9篇，撰写《中国学科发展战略.光化学》第五章第三节（约1.8万余字）。指导博士研究生2人，硕士研究生4人，已协助培养毕业博士3名、硕士3名。