Case Western Reserve University, Biomedical Engineering, Cleveland, Ohio 44106, USA.
Biomacromolecules. 2012 May 14;13(5):1495-502. doi: 10.1021/bm300192t. Epub 2012 Apr 16.
Platelet-mimetic synthetic hemostats are highly attractive in transfusion medicine. To this end, past research reports have described particles that either amplify platelet aggregation or mimic platelet adhesion. However, a construct design that effectively combines both functionalities has not been reported. Here we describe the design of a liposomal construct simultaneously surface-decorated with three peptides (a vWF-binding peptide (VBP), a collagen-binding peptide (CBP), and an active platelet clustering cyclic-RGD (cRGD) peptide), that can integrate platelet-mimetic dual hemostatic activities of adhesion and aggregation. We first demonstrate that surface-immobilized cRGD-liposomes are capable of aggregating activated platelets onto themselves. Subsequently, we demonstrate that hetero-multivalent liposomes bearing VBP, CBP, and cRGD, when introduced in flow with ≈ 20,000 activated platelets per microliter, are capable of adhering to vWF/collagen surfaces and promoting the recruitment/aggregation of platelets onto themselves. We envision that optimizing this construct can lead to a highly refined synthetic hemostat design for potential application in transfusion medicine.
血小板模拟合成止血剂在输血医学中极具吸引力。为此，过去的研究报告描述了能够放大血小板聚集或模拟血小板黏附的颗粒。然而，尚未有报道设计出能够有效结合这两种功能的构建体。在这里，我们描述了一种脂质体构建体的设计，该构建体同时表面修饰有三种肽（一种 vWF 结合肽（VBP）、一种胶原蛋白结合肽（CBP）和一种活性血小板聚集环精氨酸-甘氨酸-天冬氨酸（cRGD）肽），可整合血小板模拟的黏附和聚集双重止血作用。我们首先证明了表面固定的 cRGD-脂质体能够将激活的血小板聚集到自身上。随后，我们证明了当每微升含有 ≈20000 个激活血小板的异多价脂质体携带 VBP、CBP 和 cRGD 时，能够黏附在 vWF/胶原蛋白表面，并促进血小板招募/聚集到自身上。我们设想，对这种构建体进行优化，可以设计出一种高度精细的合成止血剂，有望在输血医学中得到应用。
