Beijing Engineering Research Center for BioNanotechnology, CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China.
School of Future Technology, University of Chinese Academy of Sciences, Beijing 100049, China.
J Am Chem Soc. 2021 Jan 27;143(3):1290-1295. doi: 10.1021/jacs.0c12016. Epub 2021 Jan 17.
Molecular profiling of tumor-derived extracellular vesicles (tEVs) holds great promise for non-invasive cancer diagnosis. However, sensitive and accurate identification of tEVs is challenged by the heterogeneity of EV phenotypes which reflect different cell origins. Here we present a DNA computation device mediated by thermophoresis for detection of tEVs. The strategy leverages the aptamer-based logic gate using multiple protein biomarkers on single EVs as the input and thermophoretic accumulation to amplify the output signals for highly sensitive and specific profiling of tEVs. Employing this platform, we demonstrate a high accuracy of 97% for discrimination of breast cancer (BC) patients and healthy donors in a clinical cohort ( = 30). Furthermore, molecular phenotyping assessed by tEVs is in concordance with the results from tissue biopsy in BC patients. The thermophoresis-mediated molecular computation on EVs thus provides new opportunities for accurate detection and classification of cancers.
肿瘤衍生细胞外囊泡 (tEVs) 的分子分析在非侵入性癌症诊断方面具有巨大的潜力。然而，由于 EV 表型的异质性反映了不同的细胞起源，因此对 tEVs 的敏感和准确识别具有挑战性。在这里，我们提出了一种由热泳介导的 DNA 计算装置，用于检测 tEVs。该策略利用基于适配体的逻辑门，将单个 EV 上的多个蛋白质生物标志物作为输入，并利用热泳积累来放大输出信号，从而对 tEVs 进行高度敏感和特异性的分析。利用该平台，我们在一个临床队列中（n=30）证明了对乳腺癌 (BC) 患者和健康供体进行区分的准确率高达 97%。此外，通过 tEVs 评估的分子表型与 BC 患者组织活检的结果一致。因此，EV 上的热泳介导的分子计算为癌症的准确检测和分类提供了新的机会。
