Fabrication of electrochemical biosensor with a CD36 aptamer and AuMoS2 heterolayer for tumor-derived exosome detection.

Breast cancer (BC), which is often diagnosed at advanced stages owing to its asymptomatic progression, presents with substantial molecular heterogeneity, leading to diverse therapeutic responses and prognostic outcomes. Among its molecular subtypes, the human epidermal growth factor receptor 2-positive/hormone receptor-negative (HER2+/HR-) phenotype displays pronounced therapeutic resistance and recurrence rate, emphasizing the need for early and accurate diagnostic strategies. In this study, we aimed to develop an electrochemical aptasensor for the detection of cluster of differentiation 36 (CD36), a lipid transporter specifically overexpressed in the HER2+/HR- subtype and functionally implicated in metabolic reprogramming. To enhance performance, gold-coated molybdenum disulfide was functionalized onto the electrode, facilitating charge transfer and signal amplification. The CD36-specific aptamer, generated through the systematic evolution of ligands by the exponential enrichment process, enabled a linear response proportional to the concentration. The biosensor exhibited high selectivity and a low limit of detection (LOD) of 0.4 pM in 10% human serum. Furthermore, its diagnostic capability using exosomes derived from HER2+/HR- cells achieves a LOD of 1.2 × 103 particles/mL, demonstrating strong clinical applicability. The proposed aptamer-integrated electrochemical biosensing platform is a noninvasive and point-of-care approach for the early diagnosis of HER2+/HR- subtype, providing insights into molecularly targeted BC diagnostics.