针对循环肿瘤细胞捕获、检测及其原位诱导凋亡的个性化“抗转移”纳米诊疗探针的构建及其临床应用探索

本项目以造成恶性肿瘤转移的关键对象--循环肿瘤细胞（CTCs）为研究对象，拟设计一种集特异性富集、荧光/SERS联合检测及原位诱导凋亡多功能于一体的个性化“抗转移”纳米诊疗探针，实现对CTCs的单细胞检测与分析。通过EpCAM抗原修饰的FePt的超顺磁性、Au纳米颗粒的优异的光学性质（SERS），实现对循环肿瘤细胞的特异性磁性富集、高灵敏的SERS检测及可视化信息采集。从理论上研究材料的磁性对SERS增强效应。研究pH值响应的FePt“化疗”和Au纳米颗粒光动力“热疗”对外周血中CTCs、临床实体瘤双重诱导凋亡效果及其机制。. 通过对本项目的实施，从分子、细胞和临床(实体瘤+CTCs)三个层次建立对临床外周血中CTCs特异性识别、富集及其原位诱导凋亡的新方法与新理论，实现肿瘤转移早期预警及其立即阻断。为临床上全血液中新型个性化“抗转移”纳米诊疗药物的研制提供科学依据与理论基础。

Circulating tumor cells (CTCs) play an important role in the initiation of metastasis. This project aims to design an individualized anti-metastatic theranostic nanoprobe with simultaneous separation, detection (SERS+ fluorescence) and in situ chemotherapy multifunctions within a single nanoconstruct for the single CTCs. Based on FePt and Au nanoparticles, the nanocomposites were successfully synthesized conjugated with the targeting EpCAM and PEG, etc. Combined with the superparamagnetic FePt with the surface-enhanced Raman scattering (SERS), the as-prepared theranostic nanoprobe is able to sensitive capture and efficient detect the single CTCs and obtain the visual information of diagnosis and therapy. Based on pH-responsive FePt "chemotherapy" and Au “photothermal therapy” dual effects, we expect to obtain the apoptotic mechanism of CTCs, which is potential for anti-metastasis nanomedicine. For the early warning and intercepting of cancer metastasis, we research the feasibility, selectivity and sensitivity of the individualized theranostic nanoprobe and establish a new method for the clinical application of capture、detection and apoptosis of single CTCs.. Through the project, we hope to develop a sensitive method that can capture, detection and in situ apoptosis the CTCs in whole blood within a single nanoconstruct to provide experimental and theoretical basis for the promising anti-metastasis clinical nanomedicine platforms.