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

Author

Listed:
  • Mingyang Li

    (Southeast University
    Nanjing Medical University)

  • Xiaorong Song

    (Southeast University)

  • Haixia Tu

    (Nanjing Medical University)

  • Jie Sun

    (Southeast University)

  • Yuanyuan Deng

    (Southeast University)

  • Bing Wang

    (Nanjing Medical University)

  • Yuhan Cai

    (Southeast University)

  • Yulian Wang

    (Nanjing Medical University)

  • Bin Li

    (Southeast University)

  • Yue Wang

    (Nanjing Medical University)

  • Xiangzheng Zhang

    (Nanjing Medical University)

  • Dong Wei

    (Southeast University)

  • Xiaoyu Yang

    (Nanjing Medical University)

  • Yueshuai Guo

    (Nanjing Medical University)

  • Xiang Li

    (Southeast University)

  • Jie Gu

    (Jiangnan University)

  • Jie Ni

    (Southeast University)

  • Yifan Zhou

    (Southeast University)

  • Zhongze Gu

    (Southeast University)

  • Zhuoying Xie

    (Southeast University)

  • Yan Li

    (Nanjing Medical University)

  • Xuejiang Guo

    (Nanjing Medical University
    Innovation Center of Suzhou Nanjing Medical University)

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.

Suggested Citation

  • 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 , 2025. "A functionally tunable magnetic nanochains platform for N-glycoproteomic analysis of extracellular vesicles from ultratrace biofluids," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63075-0
    DOI: 10.1038/s41467-025-63075-0
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