Target-Induced On-Protein Clustering of Metal Peptide Enables Low Overpotential Water Splitting for Early Detection of Non-Small-Cell Lung Cancer

Abstract

This study presents a novel method for the early detection of non-small-cell lung cancer (NSCLC) by employing target-induced on-protein clustering of metal–peptide complexes to facilitate low overpotential water splitting. The approach utilizes a designed peptide molecular probe composed of an EGFR-targeting motif and a copper-chelating tetrapeptide. Upon interaction with the epidermal growth factor receptor (EGFR) and divalent copper ions, the peptide probe forms a stable complex that undergoes on-protein clustering. This clustering significantly amplifies the electrochemical signal through enhanced dityrosine cross-linking and subsequent water splitting, achieving low overpotential for detection. The method was validated using clinical tissue samples and demonstrated improved sensitivity and specificity compared with traditional detection methods. This technique holds promise for earlier and more accurate diagnosis of NSCLC, leveraging the unique properties of metal–peptide interactions and electrochemical signal amplification.