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Nano-anticoagulant based on carrier-free low molecular weight heparin and octadecylamine with an albumin shuttling effect

Author

Listed:
  • Jae-Hyeon Lee

    (Konkuk University
    Konkuk University)

  • Hansol Lim

    (Konkuk University)

  • Gaeun Ma

    (Konkuk University)

  • Seho Kweon

    (Seoul National University
    Chonnam National University)

  • Seong Jin Park

    (Seoul National University)

  • Minho Seo

    (Konkuk University
    Konkuk University)

  • Jun-Hyuck Lee

    (Konkuk University)

  • Seong-Bin Yang

    (Konkuk University)

  • Han-Gil Jeong

    (Seoul National University Bundang Hospital, Seoul National University College of Medicine)

  • Jooho Park

    (Konkuk University
    Konkuk University)

Abstract

Low-molecular-weight heparin (LMWH), derived from unfractionated heparin (UFH), has enhanced anticoagulant efficacy, long duration of action, and extended half-life. Patients receiving LMWH for preventive therapies would strongly benefit from its long-term effects, however, achieving this is challenging. Here, we design and evaluate a nanoengineered LMWH and octadecylamine conjugate (LMHO) that can act for a long time while maintaining close to 97 ± 3% of LMWH activity via end-specific conjugation of the reducing end of LMWH. LMHO can self-assemble into nanoparticles with an average size of 105 ± 1.7 nm in water without any nanocarrier and can be combined with serum albumin, resulting in a lipid-based albumin shuttling effect. Such molecules can circulate in the bloodstream for 4–5 days. We corroborate the self-assembly capability of LMHO and its interaction with albumin through molecular dynamics (MD) simulations and transmission electron microscopy (TEM) analysis. This innovative approach to carrier-free polysaccharide delivery, enhanced by nanoengineered albumin shuttling, represents a promising platform to address limitations in conventional therapies.

Suggested Citation

  • Jae-Hyeon Lee & Hansol Lim & Gaeun Ma & Seho Kweon & Seong Jin Park & Minho Seo & Jun-Hyuck Lee & Seong-Bin Yang & Han-Gil Jeong & Jooho Park, 2024. "Nano-anticoagulant based on carrier-free low molecular weight heparin and octadecylamine with an albumin shuttling effect," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50819-7
    DOI: 10.1038/s41467-024-50819-7
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    1. Mohammad Peydayesh & Sabrina Kistler & Jiangtao Zhou & Viviane Lutz-Bueno & Francesca Damiani Victorelli & Andréia Bagliotti Meneguin & Larissa Spósito & Tais Maria Bauab & Marlus Chorilli & Raffaele , 2023. "Amyloid-polysaccharide interfacial coacervates as therapeutic materials," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    2. Huanzhen Ni & Marine Z. C. Hatit & Kun Zhao & David Loughrey & Melissa P. Lokugamage & Hannah E. Peck & Ada Del Cid & Abinaya Muralidharan & YongTae Kim & Philip J. Santangelo & James E. Dahlman, 2022. "Piperazine-derived lipid nanoparticles deliver mRNA to immune cells in vivo," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
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