Title: Tracing Tumor‐derived Exosomal PD‐L1 by Dual‐aptamer Activated Proximity‐induced Droplet Digital PCR

Authors: Bingqian Lin, Tian Tian, Yinzhu Lu, Dan Liu, Mengjiao Huang, Lin Zhu, Zhi Zhu, Yanling Song, Chaoyong Yang*

Abstract: Tumor‐derived exosomal proteins have emerged as promising biomarkers for cancer diagnosis, but the quantitation accuracy is severely 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 precise quantitative analysis of tumor‐derived exosomal PD‐L1 (Exo‐PD‐L1). Taking advantage of 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 effectively 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. Overall, TRACER strategy holds great potential for analysis of different subtypes of exosomes, unprecedented capability for converting exosomes into reliable clinical indicators and exploring the biological functions of exosomes.

Full-Link: https://onlinelibrary.wiley.com/doi/10.1002/anie.202015628