Novel Platelet Substitutes: Disk-Shaped Biodegradable Nanosheets and their Enhanced Effects on Platelet Aggregation
Novel Platelet Substitutes: Disk-Shaped Biodegradable Nanosheets and their Enhanced Effects on Platelet Aggregation
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DOI：
10.1021/bc900325w
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发表时间：
2009-10-01
影响因子：
4.7
通讯作者：
Takeoka, Shinji
中科院分区：
文献类型：
--
作者：
Okamura, Yosuke;Fukui, Yoshihito;Takeoka, Shinji
我们已经研究了在其表面携带十二肽HHLGGAKQAGDV （H12）作为血小板替代品的生物相容性球形载体。该肽是纤维蛋白原γ链羧基末端序列（γ 400-411），特异性识别活化血小板上的活性形式的糖蛋白IIb/IIIa。我们的目的是评估制造一种新型血小板替代品的可能性，该替代品由具有大接触面积的圆盘状纳米片组成，而不是传统的小接触面积球形载体。将新的H12肽偶联到由可生物降解的聚（D， l -丙交酯-羟基乙酸酯）（PLGA）制成的独立纳米片的表面。这些H12-PLGA纳米片被制备在SiO2衬底上3 μ m的圆盘状疏水十八烷基区上。通过比较，还制备了具有相同表面积和H12共轭数的球形H12- plga微粒子。在流动条件下，H12-PLGA纳米片与粘附在胶原表面的活化血小板特异性相互作用，并以两倍于H12-PLGA微颗粒的速率形成血小板血栓。因此，H12-PLGA纳米片可能是治疗严重血小板减少症患者出血的一种合适的新型血小板替代药物。
We have studied biocompatible spherical carriers carrying a dodecapeptide, HHLGGAKQAGDV (H12), on their surface as platelet substitutes. This peptide is a fibrinogen gamma-chain carboxy-terminal sequence (gamma 400-411) 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. ne 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 mu m 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.