Clinical Evaluation of the HER2 Extracellular Domain in Breast Cancer Patients by Herceptin-Encapsulated Gold Nanocluster Probe-Based Electrochemiluminescence Immunoassay

The extracellular domain (ECD) of human epidermal growth factor receptor 2 (HER2) serves as a promising biomarker for the early diagnosis and treatment of breast cancer (BC). However, due to the heterogeneity of tumors, assessing HER2 status through a core needle biopsy presents significant challenges. In this study, we propose a facile and high-performance electrochemiluminescence immunoassay (ECLIA) platform utilizing a herceptin-encapsulated gold nanoclusters (HER-AuNCs)/(diisopropylamino)ethanol (DIPEA-OH) ECL system for the clinical evaluation of HER2 ECD in BC patients. The two-in-one HER-AuNCs ECL probes integrate the immunological recognition capabilities of HER with the ECL performance of AuNCs. Coupled with the low-potential and high ECL intensity of the HER-AuNCs/DIPEA-OH system, this ECL biosensing platform offers advantages in simplicity, high sensitivity, specificity, and sample saving. Consequently, the proposed ECLIA method enables ultrasensitive detection of HER2 in the range of 0.05–10 ng/mL with a detection limit of 11 pg/mL. Notably, the serum HER2 (sHER2) ECD ECLIA analytical strategy demonstrates strong correlation with tissue HER2 expression in clinical specimens. Furthermore, the sHER2 ECD ECLIA method effectively identifies individuals with HER2-negative status within the low HER2 expression population, thereby providing enhanced guidance for treatment decisions involving antibody–drug conjugates (ADC) in BC patients. Thus, the combined diagnostic approach proposed in this work accurately differentiates between HER2-positive, HER2-negative, and low-expression BC patients, facilitating informed, clinically personalized treatment decisions.