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

Bioconjug Chem. 2009 Oct 21;20(10):1958-65. doi: 10.1021/bc900325w. Epub 2009 Sep 29.


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 SiO(2) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Artificial Cells* / chemistry
  • Artificial Cells* / metabolism
  • Artificial Cells* / ultrastructure
  • Blood Platelets / metabolism*
  • Fibrinogen / chemistry*
  • Hemorrhage / therapy
  • Humans
  • Lactic Acid / chemistry*
  • Nanostructures / chemistry*
  • Nanostructures / therapeutic use
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / pharmacology*
  • Platelet Activation / drug effects*
  • Platelet Aggregation / drug effects*
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Silicon Dioxide / chemistry*
  • Thrombocytopenia / therapy
  • Thrombosis


  • Oligopeptides
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Silicon Dioxide
  • Fibrinogen