Novel platelet substitutes: Disk-shaped biodegradable nanosheets and their enhanced effects on platelet aggregation

Yosuke Okamura, Yoshihito Fukui, Koki Kabata, Hidenori Suzuki, Makoto Handa, Yasuo Ikeda, Shinji Takeoka

    Research output: Contribution to journalArticle

    27 Citations (Scopus)

    Abstract

    We have studied biocompatible spherical carriers carrying a dodecapeptide, HHLGGAKQAGDV (H12), on their surface as platelet substitutes. This peptide is a fibrinogen γ-chain carboxy-terminal sequence (γ400-411) and specifically recognizes the active form of glycoprotein IIb/IIIa on activated platelets. Our purpose is to assess the possibility of making a novel platelet substitute consisting of disk-shaped nanosheets having a large contact area for the targeting site, rather than conventional small contact area spherical carriers. The H12 peptide was conjugated to the surface of the free-standing nanosheets made of biodegradable poly(D,L-lactide-co-glycolide) (PLGA). These H12-PLGA nanosheets were fabricated onto 3 μm disk-shaped patterned hydrophobic octadecyl regions on a SiO2 substrate. By way of comparison, spherical H12-PLGA microparticles with the same surface area and conjugation number of H12 were also prepared. The resulting H12-PLGA nanosheets specifically interacted with the activated platelets adhered on the collagen surface at twice the rate of the H12-PLGA microparticles under flow conditions, and showed platelet thrombus formation in a two-dimensional spreading manner. Thus, H12-PLGA nanosheets might be a suitable candidate novel platelet alternative substitute for infused human platelet concentrates for the treatment of bleeding in patients with severe thrombocytopenia.

    Original languageEnglish
    Pages (from-to)1958-1965
    Number of pages8
    JournalBioconjugate Chemistry
    Volume20
    Issue number10
    DOIs
    Publication statusPublished - 2009 Oct 21

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    ASJC Scopus subject areas

    • Biotechnology
    • Bioengineering
    • Organic Chemistry
    • Pharmaceutical Science
    • Biomedical Engineering
    • Pharmacology

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