Clinical Evaluation\nof the HER2 Extracellular Domain\nin Breast Cancer Patients by Herceptin-Encapsulated Gold Nanocluster\nProbe-Based Electrochemiluminescence Immunoassay

The extracellular domain (ECD) of human epidermal growth\nfactor\nreceptor 2 (HER2) serves as a promising biomarker for the early diagnosis\nand treatment of breast cancer (BC). However, due to the heterogeneity\nof tumors, assessing HER2 status through a core needle biopsy presents\nsignificant challenges. In this study, we propose a facile and high-performance\nelectrochemiluminescence immunoassay (ECLIA) platform utilizing a\nherceptin-encapsulated gold nanoclusters (HER-AuNCs)/(diisopropylamino)ethanol\n(DIPEA-OH) ECL system for the clinical evaluation of HER2 ECD in BC\npatients. The two-in-one HER-AuNCs ECL probes integrate the immunological\nrecognition capabilities of HER with the ECL performance of AuNCs.\nCoupled with the low-potential and high ECL intensity of the HER-AuNCs/DIPEA-OH\nsystem, this ECL biosensing platform offers advantages in simplicity,\nhigh sensitivity, specificity, and sample saving. Consequently, the\nproposed ECLIA method enables ultrasensitive detection of HER2 in\nthe range of 0.05–10 ng/mL with a detection limit of 11 pg/mL.\nNotably, the serum HER2 (sHER2) ECD ECLIA analytical strategy demonstrates\nstrong correlation with tissue HER2 expression in clinical specimens.\nFurthermore, the sHER2 ECD ECLIA method effectively identifies individuals\nwith HER2-negative status within the low HER2 expression population,\nthereby providing enhanced guidance for treatment decisions involving\nantibody–drug conjugates (ADC) in BC patients. Thus, the combined\ndiagnostic approach proposed in this work accurately differentiates\nbetween HER2-positive, HER2-negative, and low-expression BC patients,\nfacilitating informed, clinically personalized treatment decisions.