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NET formation-mediated in situ protein delivery to the inflamed central nervous system

Author

Listed:
  • Yina Wu

    (Seoul National University)

  • Jinwon Park

    (Seoul National University)

  • Quoc-Viet Le

    (Ton Duc Thang University)

  • Junho Byun

    (Sookmyung Women’s University)

  • Jaehyun Choi

    (Seoul National University)

  • Enzhen Xu

    (Seoul National University)

  • Jaiwoo Lee

    (Seoul National University
    Korea University)

  • Yu-Kyoung Oh

    (Seoul National University)

Abstract

Delivering protein drugs to the central nervous system (CNS) is challenging due to the blood-brain and blood-spinal cord barrier. Here we show that neutrophils, which naturally migrate through these barriers to inflamed CNS sites and release neutrophil extracellular traps (NETs), can be leveraged for therapeutic delivery. Tannic acid nanoparticles tethered with anti-Ly6G antibody and interferon-β (aLy6G-IFNβ@TLP) are constructed for targeted neutrophil delivery. These nanoparticles protect interferon-β from reactive oxygen species and preferentially accumulate in neutrophils over other immune cells. Upon encountering inflammation, neutrophils release the nanoparticles during NET formation. In the female mouse model of experimental autoimmune encephalomyelitis, intravenous administration of aLy6G-IFNβ@TLP reduce disease progression and restore motor function. Although this study focuses on IFNβ and autoimmune encephalomyelitis, the concept of hitchhiking neutrophils for CNS delivery and employing NET formation for inflamed site-specific nanoparticle release can be further applied for delivery of other protein drugs in the treatment of neurodegenerative diseases.

Suggested Citation

  • Yina Wu & Jinwon Park & Quoc-Viet Le & Junho Byun & Jaehyun Choi & Enzhen Xu & Jaiwoo Lee & Yu-Kyoung Oh, 2024. "NET formation-mediated in situ protein delivery to the inflamed central nervous system," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54817-7
    DOI: 10.1038/s41467-024-54817-7
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    References listed on IDEAS

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    1. Alicia S. Wilson & Katrina L. Randall & Jessica A. Pettitt & Julia I. Ellyard & Antje Blumenthal & Anselm Enders & Benjamin J. Quah & Tobias Bopp & Christopher R. Parish & Anne Brüstle, 2022. "Neutrophil extracellular traps and their histones promote Th17 cell differentiation directly via TLR2," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Carmen Gasca-Salas & Beatriz Fernández-Rodríguez & José A. Pineda-Pardo & Rafael Rodríguez-Rojas & Ignacio Obeso & Frida Hernández-Fernández & Marta Álamo & David Mata & Pasqualina Guida & Carlos Ordá, 2021. "Blood-brain barrier opening with focused ultrasound in Parkinson’s disease dementia," Nature Communications, Nature, vol. 12(1), pages 1-7, December.
    3. Hong-Gyun Lee & Joseph M. Rone & Zhaorong Li & Camilo Faust Akl & Seung Won Shin & Joon-Hyuk Lee & Lucas E. Flausino & Florian Pernin & Chun-Cheih Chao & Kilian L. Kleemann & Lena Srun & Tomer Illouz , 2024. "Disease-associated astrocyte epigenetic memory promotes CNS pathology," Nature, Nature, vol. 627(8005), pages 865-872, March.
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