Enrichmentand Detection of HER2-Expressing ExtracellularVesicles Based on DNA Tetrahedral Nanostructures: A New Strategy forLiquid Biopsy in Breast Cancer

Extracellular vesicles (EVs) play a crucial role as important mediators of intercellular communication in the progression of tumors. The capture and analysis of tumor-derived EVs offer new possibilities for the application of cancer liquid biopsies. This study aims to construct a DNA tetrahedral nanostructure that specifically recognizes HER2 and CD63, enabling the effective enrichment and detection of HER2-expressing EVs (HEVs). We enriched HEVs from cell lines and 13 random clinical samples and validated their characteristics by dynamic light scattering, transmission electron microscopy, and Western blotting. Further, we detected HEVs levels in clinical samples. The HEVs levels in HER2-positive breast cancer patients were significantly higher than those in healthy/benign controls (mean, 4.737 vs 4.160 vs 4.144 U/μL, <i>P</i> < 0.0001), displaying a concentration gradient across different HER2 expression levels. This study establishes an approach for HEV detection, thus providing a new tool for the diagnosis of HER2-positive breast cancer.