Novel Platelet Substitutes: Disk-Shaped Biodegradable Nanosheets and their Enhanced Effects on Platelet Aggregation

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• 作者：Yosuke Okamura ; Yoshihito Fukui ; Koki Kabata ; Hidenori Suzuki ; Makoto Handa ; Yasuo Ikeda ; Shinji Takeoka
• 刊名：Bioconjugate Chemistry
• 出版年：2009
• 出版时间：October 21, 2009
• 年：2009
• 卷：20
• 期：10
• 页码：1958-1965
• 全文大小：268K
• 年卷期：v.20,no.10(October 21, 2009)
• ISSN：1520-4812

文摘

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.