“靶向多肽”介导的多功能探针：癌细胞的元素质谱和时间分辨荧光光谱二维分析

循环系统（如血液）中痕量肿瘤细胞（CTCs）的检测/定量对"癌症早期诊断"具有重要意义。本研究课题从设计合成集肿瘤细胞识别基团、光学和质谱报告基团于一体的"多功能探针"入手，发展血液中痕量CTCs的选择性高灵敏二维光学和质谱检测/定量方法。利用特定氨基酸序列的多肽（靶向多肽）与肿瘤细胞表面/内部过表达的蛋白受体/蛋白酶分子的特异性相互作用识别肿瘤细胞；利用镧系元素的长寿命发光特性和电感耦合等离子体质谱（ICP-MS）超灵敏准确检测/定量镧系元素的能力对肿瘤细胞进行二维光学和质谱检测/定量。肿瘤细胞过表达蛋白酶的靶向多肽底物的设计合成、肿瘤细胞表面蛋白受体的靶向多肽的筛选和化学修饰、"天线化合物"与"镧系元素"的匹配耦合以及它们的合理化学组装是开展血液中痕量CTCs的选择性高灵敏二维分析方法学研究过程中的核心问题，也是决定CTCs光学和质谱分析成败的关键因素，需要系统深入的研究。

Rare circulating tumour cells (CTCs) in blood are effective indicators of cancer at an early stage, their detection and quantification are thus significant for early diagnosis of cancer. This project aims to develop a two-dimensional analytical method for specific and highly sensitive determination of CTCs in blood using inductively coupled plasma mass spectrometry (ICP-MS) and time-resolved fluorescence spectrometry (TR-FS) based on a novel trifunctional probe. The trifunctional probe consists of a homing group (a homing peptide) to target CTCs, and a reporting group to readout CTCs. The reporting group has dual functions that emits long-life fluorescence (which can be detected using TR-FS) from lanthanide-based complex excited by FRET from a suitable antenna-compound, and the lanthanide labeled on CTCs can also be determined using ICP-MS, achieving two-dimensional specific and highly sensitive analysis of targeted CTCs. Design and synthesis or screen and chemical modification of a homing peptide toward the protease or the protein receptor overexpressed in or on tumour cells, and coupling and conjugation of the antenna-compound and the lanthanide-based complex as well as the chemically assembly of them are key issues, which determine the success of the proposed two-dimensional analysis of CTCs, and need a systematic and intensive study.