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. 2021 Mar 29;60(14):7582-7586.
doi: 10.1002/anie.202015628. Epub 2021 Feb 25.

Tracing Tumor-Derived Exosomal PD-L1 by Dual-Aptamer Activated Proximity-Induced Droplet Digital PCR

Bingqian Lin  1 , Tian Tian  2 , Yinzhu Lu  1 , Dan Liu  3 , Mengjiao Huang  1 , Lin Zhu  1 , Zhi Zhu  1 , Yanling Song  1 , Chaoyong Yang  1   4
Affiliations

Tracing Tumor-Derived Exosomal PD-L1 by Dual-Aptamer Activated Proximity-Induced Droplet Digital PCR

Bingqian Lin et al. Angew Chem Int Ed Engl. .

Abstract

Tumor-derived exosomal proteins have emerged as promising biomarkers for cancer diagnosis, but the quantitation accuracy is hindered by large numbers of normal cell-derived exosomes. Herein, we developed a dual-target-specific aptamer recognition activated in situ connection system on exosome membrane combined with droplet digital PCR (ddPCR) (TRACER) for quantitation of tumor-derived exosomal PD-L1 (Exo-PD-L1 ). Leveraging the high binding affinity of aptamers, excellent selectivity of dual-aptamer recognition, and the high sensitivity of ddPCR, this method exhibits significant sensitivity and selectivity for tracing tumor-derived Exo-PD-L1 in a wash-free manner. Due to the excellent sensitivity, the level of tumor-derived Exo-PD-L1 detected by TRACER can distinguish cancer patients from healthy donors, and for the first time was identified as a more reliable tumor diagnostic marker than total Exo-PD-L1 . The TRACER strategy holds great potential for converting exosomes into reliable clinical indicators and exploring the biological functions of exosomes.

Keywords: aptamers; exosomes; immunotherapy; proximity ligation assay.

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