Development of fibrinogen γ-chain peptide-coated, adenosine diphosphate-encapsulated liposomes as a synthetic platelet substitute
Development of fibrinogen γ-chain peptide-coated, adenosine diphosphate-encapsulated liposomes as a synthetic platelet substitute
复制标题
DOI：
10.1111/j.1538-7836.2008.03269.x
复制
发表时间：
2009-03-01
影响因子：
10.4
通讯作者：
Handa, M.
中科院分区：
文献类型：
--
作者：
Okamura, Y.;Takeoka, S.;Handa, M.
背景：十二肽HHLGGAKQAGDV(H12)对应于纤维蛋白原-伽马链羧基末端序列(Gamma 400-411)，是血小板GPIIb/IIIa复合体的特异性配体结合部位。我们评估了H12包裹的纳米颗粒(聚合白蛋白或脂质体)作为支持血小板功能的合成产品。目的：通过将二磷酸腺苷(ADP)包裹到脂质体[H12-(ADP)-脂质体]中，增强H12包被颗粒作为血小板替代物的止血能力。方法和结果：H12-(ADP)脂质体通过GPIIb/IIIa与活化的血小板选择性相互作用，通过释放依赖聚集的ADP来增强激动剂诱导的血小板聚集。当静脉注射到大鼠体内时，根据计算机断层扫描的分析，脂质体很容易靶向血管损伤的部位。事实上，与新鲜的血小板相比，脂质体在纠正布舒坦诱导的血小板减少兔模型中延长的出血时间方面表现出了相当大的止血能力。此外，脂质体对正常兔的循环血小板无激活或聚集作用。结论：H12-(ADP)-脂质体是一种很有前途的血小板替代物，仅由合成材料制成，在体内通过血管损伤部位残留的血小板增强原发血栓的形成而发挥止血作用，但在循环中不起作用。
Background: The dodecapeptide HHLGGAKQAGDV (H12), corresponding to the fibrinogen gamma-chain carboxy-terminal sequence (gamma 400-411), is a specific binding site of the ligand for platelet GPIIb/IIIa complex. We have evaluated H12-coated nanoparticles (polymerized albumin or liposome) as platelet function-supporting synthetic products. Objectives: To strengthen the hemostatic ability of H12-coated particles as a platelet substitute, we exploited installation of a drug delivery function by encapsulating adenosine diphosphate (ADP) into liposomes [H12-(ADP)-liposomes]. Methods and results: Via selective interaction with activated platelets through GPIIb/IIIa, H12-(ADP)-liposomes were capable of augmenting agonist-induced platelet aggregation by releasing ADP in an aggregation-dependent manner. When intravenously injected into rats, liposomes were readily targeted to sites of vascular injury as analyzed on computed tomography. In fact, comparable to fresh platelets, liposomes exhibited considerable hemostatic ability for correcting prolonged bleeding time in a busulphan-induced thrombocytopenic rabbit model. In addition, the liposomes showed no activating or aggregating effects on circulating platelets in normal rabbits. Conclusion: H12-(ADP)-liposome may thus offer a promising platelet substitute, being made with only synthetic materials and exerting hemostatic functions in vivo via reinforcement of primary thrombus formation by residual platelets in thrombocytopenia at sites of vascular injury, but not in circulation.