Metal Cluster-Based Electrochemical Biosensing System for Detecting Epithelial-to-Mesenchymal Transition.
Metal Cluster-Based Electrochemical Biosensing System for Detecting Epithelial-to-Mesenchymal Transition.
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DOI：
10.1021/acssensors.1c00339
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发表时间：
2021-05
期刊：
影响因子：
8.9
通讯作者：
Ying Han;Cuicui Qiu;Jiaojiao Li;Fuping Gao;Q. Yuan;Yuhua Tang;Wenchao Niu;Xiayan Wang;Xueyun Gao;Liang Gao
中科院分区：
文献类型：
--
作者：
Ying Han;Cuicui Qiu;Jiaojiao Li;Fuping Gao;Q. Yuan;Yuhua Tang;Wenchao Niu;Xiayan Wang;Xueyun Gao;Liang Gao
n -钙粘蛋白是上皮-间质转化（EMT）进展的重要肿瘤生物标志物，可识别恶性肿瘤细胞的侵袭和转移。尽管许多努力已经致力于n -钙粘蛋白的定量检测，但在完整细胞水平上分析感兴趣的蛋白质的努力很少。本文开发了一种基于金属簇的电化学生物传感系统，用于测定肿瘤细胞EMT过程中N-cadherin的表达水平。具体地说，一个具有独特序列和功能的肽被设计为还原剂和锚，以精确的方式合成金属簇。因此，肽修饰的金属团簇具有n-钙粘蛋白靶向、光致发光和电催化性质。特别是，氧化还原活性金属团簇作为电子传递介质和电子导体，用于增强电化学传感。这些有利的特性使其成为一种快速、灵敏、可靠的全细胞生物传感器，它集成了荧光和电化学信号。这种细胞传感器可以准确量化至少5000个肿瘤细胞上N-cadherin的表达水平。此外，随着EMT的进展，模型癌细胞的电流信号逐渐增加，表明肿瘤细胞类型的进化。我们的研究代表了先进的生物探针和分析方法，用于准确定量的生物标志物来识别肿瘤进展。
N-cadherin serves as an important oncobiomarker of epithelial-to-mesenchymal transition (EMT) progression, which identifies invasion and metastasis of malignant tumor cells. Although many efforts have been devoted to quantitative detection of N-cadherin, efforts to analyzing the protein of interest at intact cellular levels are scarce. Herein, a metal cluster-based electrochemical biosensing system is developed to determine the expressing levels of N-cadherin during the EMT process of tumor cells. To be specific, a peptide with a unique sequence and function is designed as a reductant and an anchor to synthesize metal clusters in a precise manner. Consequently, peptide-modified metal clusters possess N-cadherin-targeting, photoluminescence, and electrocatalytic properties. Especially, the redox-active metal clusters function as both an electron-transfer mediator and an electronic conductor for enhanced electrochemical sensing. These favorable features enable them as a rapid, sensitive, and reliable whole-cell biosensor, which integrates the fluorescence and electrochemical signals. This cytosensor can accurately quantify the expression levels of N-cadherin on at least 5000 tumor cells. Further, the current signals of model cancer cells gradually increase with EMT progression, indicating tumor cell-type evolution. Our study represents the advanced bioprobe and analytical methods for accurate quantitation of a biomarker to identify tumor progression.