A functionally tunable magnetic nanochains platform for N-glycoproteomic analysis of extracellular vesicles from ultratrace biofluids
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, R<sub>8</sub>) enable efficient EV isolation, followed by on-chain hydrolysis to expose PEG<sub>2000</sub> 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.
Authors
- Xiaorong Song (ORCID: https://orcid.org/0000-0001-5484-0978)
- Jie Ni
- Zhongze Gu (ORCID: https://orcid.org/0000-0001-8926-7710)
- Jie Gu (ORCID: https://orcid.org/0000-0003-2104-9367)
- Yifan Zhou (ORCID: https://orcid.org/0000-0002-9836-6355)
- Zhuoying Xie (ORCID: https://orcid.org/0000-0003-3534-1924)
- Xuejiang Guo (ORCID: https://orcid.org/0000-0002-0475-5705)
- Yueshuai Guo (ORCID: https://orcid.org/0000-0002-5950-4591)
- Jie Sun (ORCID: https://orcid.org/0000-0002-5642-0560)
- Haixia Tu
- Xiangzheng Zhang
- Bin Li (ORCID: https://orcid.org/0000-0002-5717-1551)
- Yue Wang (ORCID: https://orcid.org/0000-0002-7670-7673)
- Yan Li (ORCID: https://orcid.org/0000-0003-0420-4222)
- Bing Wang (ORCID: https://orcid.org/0000-0003-0684-2789)
- Yulian Wang
- Xiaoyu Yang (ORCID: https://orcid.org/0000-0002-6411-8935)
- Xiang Li (ORCID: https://orcid.org/0000-0001-9414-0298)
- Yanan Cai
- Yifei Deng (ORCID: https://orcid.org/0009-0005-1530-1273)
- Mingyang Li (ORCID: https://orcid.org/0000-0001-7723-951X)
- Dong Wei
Institutions
- Jiangnan University (CN)
- Soochow University (CN)
- Southeast University (CN)
- Nanjing Medical University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-08-16
- DOI
- https://doi.org/10.1038/s41467-025-63075-0
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- Government of Jiangsu Province
- Southeast University
- National Key Research and Development Program of China
- Fundamental Research Funds for the Central Universities