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用于肿瘤衍生外泌体分离与分析的同质磁荧光纳米传感器

Homogenous Magneto-Fluorescent Nanosensor for Tumor-Derived Exosome Isolation and Analysis.

作者信息

Li Bo, Pan Weilun, Liu Chunchen, Guo Jingyun, Shen Jianlei, Feng Junjie, Luo Tingting, Situ Bo, Zhang Ye, An Taixue, Xu Chunzuan, Zheng Wancheng, Zheng Lei

机构信息

Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

出版信息

ACS Sens. 2020 Jul 24;5(7):2052-2060. doi: 10.1021/acssensors.0c00513. Epub 2020 Jul 14.

Abstract

Tumor-derived exosomes carrying unique surface proteins have shown great promise as novel biomarkers for liquid biopsies. However, point-of-care analysis for tumor-derived exosomes in the blood with low-cost and easy processing is still challenging. Herein, we develop an integrated approach, homogenous magneto-fluorescent exosome (hMFEX) nanosensor, for rapid and on-site tumor-derived exosomes analysis. Tumor-derived exosomes are captured immunomagnetically, which further initiates the aptamer-triggered assembly of DNA three-way junctions in homogenous solution containing aggregation-induced emission luminogens and graphene oxide, resulting in an amplified fluorescence signal. By integrating magnetic isolation and enhanced fluorescence measurement, the hMFEX nanosensor detects tumor-derived exosomes in the dynamic range spanning 5 orders of magnitude with high specificity, and the limit of detection is 6.56 × 10 particles/μL. Analyzing tumor-derived exosomes in limited volume plasma from breast cancer patients demonstrates the excellent clinical diagnostic efficacy of the hMFEX nanosensor. This study provides new insights into the point-of-care testing of tumor-derived exosomes for cancer diagnostics.

摘要

携带独特表面蛋白的肿瘤衍生外泌体作为液体活检的新型生物标志物显示出巨大潜力。然而,对血液中肿瘤衍生外泌体进行低成本且易于处理的即时检测分析仍然具有挑战性。在此,我们开发了一种集成方法,即同质磁荧光外泌体(hMFEX)纳米传感器,用于快速、现场分析肿瘤衍生外泌体。肿瘤衍生外泌体通过免疫磁捕获,这进一步在含有聚集诱导发光剂和氧化石墨烯的同质溶液中引发适体触发的DNA三向连接体组装,从而产生放大的荧光信号。通过整合磁分离和增强荧光测量,hMFEX纳米传感器在跨越5个数量级的动态范围内以高特异性检测肿瘤衍生外泌体,检测限为6.56×10颗粒/μL。对乳腺癌患者有限体积血浆中的肿瘤衍生外泌体进行分析,证明了hMFEX纳米传感器具有出色的临床诊断效能。本研究为肿瘤衍生外泌体用于癌症诊断的即时检测提供了新的见解。

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