Signal-amplified fluorescent biosensing for exosomes analysis and exosomes-driven high-throughput screening of traditional Chinese medicine.

Abstract

Exosomes, extracellular vesicles involved in intercellular communication and disease progression, have emerged as promising therapeutic targets and drug delivery vehicles. Targeting exosomes for drug screening offers significant potential in developing treatments for cancer. However, conventional methods for exosome-based drug discovery often lack sensitivity, specificity. To address these limitations, we propose a signal-amplified fluorescent biosensing (SAFB) system designed to screen drugs by specifically targeting exosomal biomarkers. This sensor integrates exosome-specific surface markers (Epithelial cell adhesion molecule (EpCAM)) with dual fluorescence amplification cascade probes (catalytic hairpin assembly (CHA), CdTe quantum dots (QDs)), enabling highly sensitive, label-free detection of exosomes and exosome-drug interactions. Moreover, SAFB is employed for high-throughput screening (HTS) to identify active compounds from Traditional Chinese Medicine (TCM). HFB-5D is screened out by inhibiting the Wnt/β-catenin signaling pathway to inhibit breast cancer growth. Overall, this work provides a versatile and promising tool for exosomes analysis and advancing exosome-related drug discovery.

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