Enrichment and Detection of HER2-Expressing Extracellular Vesicles Based on DNA Tetrahedral Nanostructures: A New Strategy for Liquid Biopsy in Breast Cancer

IF 6.7 1区化学 Q1 CHEMISTRY, ANALYTICAL Analytical Chemistry Pub Date : 2025-03-21 DOI:10.1021/acs.analchem.4c06417

Feng Xu, Ke Wang, Chi Xu, Jingtong Xu, Chengjun Zhu, Ye Zhu, Chuandong Zhu, Wenwen Zhang, Jian Zhang, Zhe Li, Xiaoxiang Guan

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Abstract

Extracellular vesicles (EVs) play a crucial role as important mediators of intercellular communication in the progression of tumors. The capture and analysis of tumor-derived EVs offer new possibilities for the application of cancer liquid biopsies. This study aims to construct a DNA tetrahedral nanostructure that specifically recognizes HER2 and CD63, enabling the effective enrichment and detection of HER2-expressing EVs (HEVs). We enriched HEVs from cell lines and 13 random clinical samples and validated their characteristics by dynamic light scattering, transmission electron microscopy, and Western blotting. Further, we detected HEVs levels in clinical samples. The HEVs levels in HER2-positive breast cancer patients were significantly higher than those in healthy/benign controls (mean, 4.737 vs 4.160 vs 4.144 U/μL, P < 0.0001), displaying a concentration gradient across different HER2 expression levels. This study establishes an approach for HEV detection, thus providing a new tool for the diagnosis of HER2-positive breast cancer.

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基于DNA四面体纳米结构的表达her2的细胞外囊泡的富集和检测：乳腺癌液体活检的新策略

细胞外囊泡（EVs）作为细胞间通讯的重要介质在肿瘤的进展中起着至关重要的作用。肿瘤源性ev的捕获和分析为癌症液体活检的应用提供了新的可能性。本研究旨在构建特异性识别HER2和CD63的DNA四面体纳米结构，实现对表达HER2的ev （hev）的有效富集和检测。我们从细胞系和13个随机临床样本中富集hev，并通过动态光散射、透射电镜和Western blotting验证其特性。此外，我们检测了临床样本中的hev水平。her2阳性乳腺癌患者的hev水平显著高于健康/良性对照组(平均：4.737 vs 4.160 vs 4.144 U/μL, P <；0.0001)，显示不同HER2表达水平的浓度梯度。本研究建立了一种检测HEV的方法，从而为her2阳性乳腺癌的诊断提供了一种新的工具。

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来源期刊

Analytical Chemistry 化学-分析化学

CiteScore

12.10

自引率

12.20%

发文量

1949

审稿时长

1.4 months

期刊介绍： Analytical Chemistry, a peer-reviewed research journal, focuses on disseminating new and original knowledge across all branches of analytical chemistry. Fundamental articles may explore general principles of chemical measurement science and need not directly address existing or potential analytical methodology. They can be entirely theoretical or report experimental results. Contributions may cover various phases of analytical operations, including sampling, bioanalysis, electrochemistry, mass spectrometry, microscale and nanoscale systems, environmental analysis, separations, spectroscopy, chemical reactions and selectivity, instrumentation, imaging, surface analysis, and data processing. Papers discussing known analytical methods should present a significant, original application of the method, a notable improvement, or results on an important analyte.