The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China.
Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China.
Angew Chem Int Ed Engl. 2021 Mar 29;60(14):7582-7586. doi: 10.1002/anie.202015628. Epub 2021 Feb 25.
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- ). 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- in a wash-free manner. Due to the excellent sensitivity, the level of tumor-derived Exo- 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- . The TRACER strategy holds great potential for converting exosomes into reliable clinical indicators and exploring the biological functions of exosomes.
肿瘤来源的外泌体蛋白已成为癌症诊断有前途的生物标志物，但由于大量正常细胞来源的外泌体，其定量准确性受到阻碍。在此，我们开发了一种在外泌体膜上结合液滴数字 PCR（ddPCR）（TRACER）的双靶特异性适体识别原位连接系统，用于定量肿瘤来源的外泌体 PD-L1（Exo-）。利用适体的高结合亲和力、双适体识别的优异选择性和 ddPCR 的高灵敏度，该方法以非洗涤的方式对肿瘤来源的 Exo-进行跟踪，具有显著的灵敏度和选择性。由于灵敏度高，TRACER 检测到的肿瘤来源的 Exo-水平可将癌症患者与健康供体区分开来，并且首次被确定为比总 Exo-更可靠的肿瘤诊断标志物。TRACER 策略有可能将外泌体转化为可靠的临床指标，并探索外泌体的生物学功能。
