A functionally tunable magnetic nanochains platform for N-glycoproteomic analysis of extracellular vesicles from ultratrace biofluids

IF 15.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2025-08-16 DOI:10.1038/s41467-025-63075-0

Mingyang Li, Xiaorong Song, Haixia Tu, Jie Sun, Yuanyuan Deng, Bing Wang, Yuhan Cai, Yulian Wang, Bin Li, Yue Wang, Xiangzheng Zhang, Dong Wei, Xiaoyu Yang, Yueshuai Guo, Xiang Li, Jie Gu, Jie Ni, Yifan Zhou, Zhongze Gu, Zhuoying Xie, Yan Li, Xuejiang Guo

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Abstract

Extracellular vesicles (EVs) carry complex glycoproteins critical mediators of disease progression and hold great potential for liquid biopsy applications. However, their low abundance presents significant analytical challenges. This study develop a versatile platform for EV N-glycoproteomic analysis (EVGpro), which enables tandem EV capture, EV protein digestion, and enrichment of N-glycopeptides. Functionalized magnetic nanochains with cell-penetrating peptides (octa-arginine, R₈) enable efficient EV isolation, followed by on-chain hydrolysis to expose PEG₂₀₀₀ for ultrasensitive glycopeptide enrichment. The streamlined EVGpro platform identified up to 17 times more EV glycoproteins than ultracentrifugation across seven biofluids, profiling 398 EV glycoproteins from just 1 μL tear. Applied to seminal plasma, EVGpro uncover disease-specific glycoprotein signatures and identified previously unreported subtypes of asthenozoospermia. This robust and scalable approach advances the sensitive detection of disease biomarkers and molecular subtypes from diverse biofluids to enable precision medicine.

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一个功能可调的磁性纳米链平台，用于超微量生物体液细胞外囊泡的n -糖蛋白组学分析

细胞外囊泡（EVs）携带复杂的糖蛋白，是疾病进展的关键介质，在液体活检应用中具有很大的潜力。然而，它们的低丰度给分析带来了重大挑战。本研究开发了EV n -糖蛋白组学分析（EVGpro）的通用平台，可实现EV捕获、EV蛋白消化和n -糖肽富集。带有细胞穿透肽（八元精氨酸，R8）的功能化磁性纳米链能够有效分离EV，然后在链上水解暴露PEG2000以进行超灵敏的糖肽富集。流线型EVGpro平台在7种生物体液中鉴定出的EV糖蛋白比超离心鉴定出的EV糖蛋白多17倍，仅从1 μL的眼泪中分析出398种EV糖蛋白。应用于精浆，EVGpro揭示了疾病特异性糖蛋白特征，并鉴定了以前未报道的弱精子症亚型。这种强大且可扩展的方法促进了对来自不同生物流体的疾病生物标志物和分子亚型的敏感检测，从而实现精准医疗。

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.