Department of Mechanical Engineering, Imperial College London, U.K.
School of Mechanical, Aerospace & Civil Engineering, University of Manchester, U.K.
Nanomedicine. 2017 May;13(4):1531-1542. doi: 10.1016/j.nano.2017.01.019. Epub 2017 Feb 24.
In this study, we investigated gold nanoparticle (AuNP) interactions in blood using thromboelastography as a rapid screening tool to monitor their influence on blood coagulation. 1.2 nM colloidal AuNPs ranging from 12 to 85 nm have no effect in the blood, however, 5 nM AuNPs demonstrate pro-thrombogenic concentration dependent effects with a reduction in clot formation. Size effects exhibit a non-linear trend with 45 and 85 nm particles resulting in a faster pro-thrombotic response. Clot strength decreased with AuNP size with the greatest reduction with 28 nm particles. We assessed AuNP interactions in the blood focusing on their biological activity. AuNP-RGD possessed pro-coagulant activities, while PEG-thiol, human fibrinogen and clopidogrel prevented blood clot formation and influenced platelet activity, and were more efficient when bound to nanocarriers than unbound ligands. Such tests could fill the knowledge gaps in thrombogenicity of NPs between in vitro test methods and predict in vivo haemocompatibility.
在这项研究中，我们使用血栓弹性描记法作为快速筛选工具，研究了金纳米粒子（AuNP）在血液中的相互作用，以监测它们对血液凝固的影响。1.2 nM 粒径为 12 至 85nm 的胶体 AuNP 对血液无影响，然而 5 nM 的 AuNP 表现出促血栓形成的浓度依赖性效应，导致血栓形成减少。尺寸效应呈非线性趋势，45nm 和 85nm 粒径的粒子导致更快的促血栓形成反应。随着 AuNP 粒径的增加，血栓强度降低，28nm 粒径的粒子降低幅度最大。我们评估了 AuNP 在血液中的相互作用，重点关注其生物学活性。AuNP-RGD 具有促凝血活性，而 PEG-巯基、人纤维蛋白原和氯吡格雷可防止血栓形成并影响血小板活性，与纳米载体结合时比未结合配体更有效。这些测试可以填补纳米粒子血栓形成性在体外测试方法和体内血液相容性预测之间的知识空白。
