Metal Cluster-Based Electrochemical Biosensing System for Detecting Epithelial-to-Mesenchymal Transition

ACS Sens. 2021 Jun 25;6(6):2290-2298. doi: 10.1021/acssensors.1c00339. Epub 2021 May 27.


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.

Keywords: N-cadherin; biosensor; epithelial-to-mesenchymal transition; in situ electrochemical analysis; metal clusters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biosensing Techniques*
  • Cadherins
  • Epithelial-Mesenchymal Transition*
  • Humans
  • Neoplasms*
  • Tumor Cells, Cultured


  • Cadherins