肿瘤小细胞外囊泡的精准检测  

Precision Detection of Tumor Small Extracellular Vesicles

作　　者：王慧静 孙蝶 王睿颖 张卉[1] Huijing Wang;Die Sun;Ruiying Wang;Hui Zhang(College of Chemistry and Materials Science,Nanjing Normal University,Nanjing 210023,China)

机构地区：[1]南京师范大学化学与材料科学学院,南京210023

出　　处：《化学进展》2024年第12期1972-1982,共11页Progress in Chemistry

基　　金：国家自然科学基金(No.22274077)资助。

摘　　要：肿瘤小细胞外囊泡是由肿瘤细胞释放的粒径小于200 nm的膜性囊泡,其表面和内部携带各种生物分子信息并参与细胞间通信,是公认的最重要的癌症液体活检物之一。肿瘤小细胞外囊泡表面含有多种蛋白,这些蛋白可以与其相对应的抗体或核酸适配体相结合,利用光学或电化学方法可以实现肿瘤小细胞外囊泡的定量检测。由于小细胞外囊泡的高度异质性和复杂性,单一生物标志物的识别容易受到外界干扰产生假阳性或假阴性信号,因此依靠单一的蛋白很难实现对肿瘤小细胞外囊泡的精准检测。同时分析多种生物标志物可以有效地解决该问题并提供更准确的癌症诊断和预后指导。本文论述了基于表面蛋白的肿瘤小细胞外囊泡的检测方法,如荧光法、比色法、电化学方法以及电致化学发光等,并从多蛋白多信号比例输出、多蛋白逻辑门的使用以及多蛋白邻近连接反应的角度重点讨论了基于表面多蛋白的小细胞外囊泡的高灵敏度的精确检测。Tumor small extracellular vesicles(sEVs)are membranous vesicles,released by tumor cells,with a particle size less than 200 nm.They carry diverse biomolecular information on their surface and inside,participating in intercellular communication and are recognized as one of the most crucial liquid biopsies for cancer.Because sEVs’surface contains a variety of proteins that can bind to corresponding antibodies or nucleic acid aptamers,quantitative detection of sEVs can be achieved through optical or electrochemical methods.However,due to the high heterogeneity and complexity of sEVs,relying on a single protein for recognition may lead to false positive or false negative signals.Therefore,accurate detection of tumor-derived sEVs requires simultaneous analysis of multiple biomarkers.Simultaneous analysis of multiple biomarkers can effectively address interference caused by phenotypic heterogeneity in sEVs and provide more accurate guidance for cancer diagnosis and prognosis.This paper focuses on the detection methods of sEVs based on surface proteins using fluorescence,colorimetry,electrochemical methods,and electrochemiluminescence techniques.It emphasizes the importance of achieving high sensitivity and accuracy in detecting sEVs through multi-protein multi-signal proportional output approaches,employing multi-protein logic gates and multi-protein proximity linking reactions.

关 键 词：肿瘤小细胞外囊泡 外泌体 液体活检 精准检测 表面多蛋白分析 

分 类 号：O657.3[理学—分析化学] R730.4[理学—化学]