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

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