Monitoring Abundance and Activity of Electrochemically Inactive Protein in a Single Cell by an Atomically Precise Metal Cluster-Based Electrochemical Sensor

The analysis of tumor metastasis-associated proteins is of vital importance for monitoring tumor evolution and evaluating therapeutic outcomes of protein-targeted drugs. However, electrochemically analyzing both the abundance and activity of these electrochemically inactive proteins in single living cells remains an unresolved challenge. Here, we develop an electrochemical sensor composed of a nanoelectrode functionalized by atomically precise metal clusters with excellent electrocatalytic activity. It enables highly selective detection of electrochemically inactive proteins associated with tumor metastasis. Via this sensor, we demonstrate the relation between cathepsin B abundance and metastatic features of tumor cells. The inherent heterogeneous protein expression among individual cells is confirmed by a quantitative manner. Additionally, this methodology allows for the assessment of cathepsin B activity in response to the antimetastatic drug exposure at a single-cell level. It deepens our understanding of cathepsin B's role in tumor metastasis and provides potential for precise evaluation of cathepsin B-targeted drugs.