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

Jae-Hyeon Lee, Hansol Lim, Gaeun Ma, Seho Kweon (), Seong Jin Park, Minho Seo, Jun-Hyuck Lee, Seong-Bin Yang, Han-Gil Jeong and Jooho Park ()
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Jae-Hyeon Lee: Konkuk University
Hansol Lim: Konkuk University
Gaeun Ma: Konkuk University
Seho Kweon: Seoul National University
Seong Jin Park: Seoul National University
Minho Seo: 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

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-50819-7

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