新型AIE探针的构筑及其在稀有肿瘤细胞成像中的应用

Bioimaging is of great importance in biomedical applications, such as drug screening, toxicology assessment, personalized medicine, and so on. Except for clinical MRI, CT, ultrasound techniques, fluorescence imaging has also been paid extensive attention due to its significant advantages, such as high sensitivity and spatial-temporal resolution, low-cost, easy operation, etc. However, conventional fluorescent dyes are prone to be quenched due to aggregates formation. AIEgens have proven to be very competitive in bioimaging, but their clinical applications are still highly demanded. Interestingly, rare tumor cells in body fluid samples (blood, pleural fluid, cerebrospinal fluid, etc.) can be evidence of presence and metastasis of early tumors, but they often involve tedious detecting steps and high professional requirements. This project will develop a series of novel AIE bioprobes with tunable emission wavelengths, high emission efficiency, good biocompatibility and photostability, as well as specificity for different cancer cells. And their clinical practicality in rare tumor cells (CTCs in the peripheral blood as a typical example) will be also studied. This project is bound to promote the developments of early diagnosis and therapy of cancers, as well as new clinical testing techniques.

生物成像在生物医学领域非常重要，如药物筛选、毒理学评估、个性化医疗等。除了临床上用的核磁共振、计算机断层扫描、超声等成像方法之外，荧光成像技术也因其高灵敏度、高时空分辨率、造价低廉、易于操作等突出优势而备受关注。然而，传统有机荧光染料在生物成像时往往会因为聚集而发生荧光猝灭。AIE材料已被证实在生物成像领域具有很强的竞争力，但是其临床应用却十分有限。引起我们兴趣的是，临床上体液样本中（如血液、胸腹水、脑脊液）的稀有肿瘤细胞可作为早期肿瘤存在、转移的有力证据，但是其检测往往步骤繁琐，专业要求也很高。因此，本项目将构建一系列新型AIE探针，赋予它们可调的发光光谱、高的发光效率、良好的生物相容性和光稳定性，以及对多种癌细胞的特异性，并将以外周血循环肿瘤细胞（CTCs）为例，实现它们对临床稀有肿瘤细胞成像。本项目将为癌症的早诊早治以及临床检验新方法的发展起到重要推动作用。

稀有肿瘤细胞是早期肿瘤存在、转移的有力证据，其检测及分析具有重要的临床意义，但其准确鉴别仍然存在挑战性。申请人围绕具有聚集诱导发光性能的新型荧光探针在稀有肿瘤细胞检测方面的应用展开了一系列研究，并取得了阶段性的研究成果。例如，基于肿瘤细胞与正常细胞的细胞核致密程度差异，建立了胸腔积液稀有肿瘤细胞鉴定新方法；运用核仁靶向的探针，探索了循环肿瘤细胞检测新方法。这些研究结果为恶性肿瘤诊断新方法的建立提供了新的思路和方法，也证实了聚集诱导发光材料在生物医学领域具有巨大的临床应用潜力和价值。在本项目的资助下，已发表标注项目号的学术论文2篇，申请中国发明专利1项，部分研究结果也在进一步完善和整理中；合作培养研究生2名（已毕业）。