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
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

Cite this

Okamura, Y., Fukui, Y., Kabata, K., Suzuki, H., Handa, M., Ikeda, Y., & Takeoka, S. (2009). Novel platelet substitutes: Disk-shaped biodegradable nanosheets and their enhanced effects on platelet aggregation. Bioconjugate Chemistry, 20(10), 1958-1965. https://doi.org/10.1021/bc900325w