Exosomes, a class of extracellular vesicles carrying the biological information of their parent cells, have emerged as one of the most promising biomarkers for the early screening and prognostic monitoring of cancer. However, the effective capture and sensitive detection of cancer cell-derived exosomes pose significant challenges due to the inevitable interference from internal environment and the limited exosome abundance in clinical samples. Herein, we proposed an aptamer-based electrochemical biosensor combining with Au nanoprobe-mediated dual signal amplification for sensitive detection of tumor-related exosomes. Benefiting from the specific recognition of CD63 aptamer (CD63 Apt), the target exosomes were efficiently captured on the gold electrode, followed by trapping the iDNA-modified Au nanoprobe, which could induce the generation of hybridization chain reaction (HCR). The long double-stranded DNA produced by HCR procedure provided numerous insertion sites to RuHex, achieving the high sensitivity for exosome detection. Under the optimal experimental conditions, this aptamer-based electrochemical biosensor for MCF-7 cancer cell-derived exosome detection exhibited a good linear range within 5 orders of magnitude (from 1.29 × 104 to 1.29 × 108 particle/mL) with a low limit of detection (LOD) to 1.65 × 103 particle/mL. Furthermore, this biosensor possessed good stability and anti-interference ability. Therefore, this analysis platform is considered as a promising candidate for the exosome-based diagnosis and prognosis of cancer in clinical applications.
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