Proximity-induced amplification cascade for accurate and sensitive colorimetric detection of tumor-derived exosomes

Abstract

Tumor-derived exosomes have garnered immense interest as potential molecular markers for noninvasive diagnosis, treatment, and prognostic evaluation of cancer. Herein, we have reported a proximity-induced amplification cascade for achieving accurate and sensitive colorimetric detection of tumor-derived exosomes. Specifically, the proximity hybridization effect triggered by the binding of two aptamers to the adjacent proteins on the surface of the target exosomes will lead to the release of the trigger strand, initiating a cascade of subsequent three-way catalytic hairpin assembly and rolling circle amplification reactions. Consequently, a substantial amount of single-strand DNA will be generated, which can bind to numerous DNA- Pt@AuNPs signal probes and be efficiently captured by the multivalent capture interface, leading to dramatically intensified colorimetric signals for sensitive detection of tumor-derived exosomes. Benefiting from the synergy of multiple signal amplification strategies, a detection limit as low as 194 particles μL⁻¹ has been achieved. In addition, the dual-molecular recognition enabled by proximity effect endows the sensing platform with excellent selectivity to distinguish target exosomes from other interfering exosomes, cell fragments and proteins. Notably, the proposed sensing platform can be successfully applied to the detection of targets in serum samples and can distinguish between MUC1/EpCAM-positive breast cancer patients from healthy individuals, highlighting its promising potential in clinical cancer diagnosis.