GW Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA; Parker H Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA.
University of Colorado, Anschutz Medical Campus, Pediatrics Hematology, Oncology, Aurora, CO; Washington University School of Medicine, St. Louis, MO.
Nanomedicine. 2021 Jul;35:102405. doi: 10.1016/j.nano.2021.102405. Epub 2021 Apr 28.
Platelet accumulation by VWF under high shear rates at the site of atherosclerotic plaque rupture leads to myocardial infarction and stroke. Current anti-platelet therapies remain ineffective for a large percentage of the population, while presenting significant risks for bleeding. We explore a novel way to inhibit arterial thrombus formation. Theoretically, a negative charge may influence the tertiary structure of VWF to favor the globular configuration by biophysical means without the use of platelet inactivating drugs. We tested this hypothesis experimentally for charged nanoparticles (CNPs) to inhibit thrombus formation in a microfluidic thrombosis assay (MTA). Several different CNPs demonstrated the ability to retard thrombotic occlusion in the MTA. A preliminary study in mice shows that thrombus stability is weaker with CNP administration and bleeding times are not markedly prolonged. The CNPs tested here show promise as a new class of antithrombotic therapies that act by biophysical means rather than biochemical pathways.
血小板在动脉粥样硬化斑块破裂部位的高剪切率下通过 vWF 聚集，导致心肌梗死和中风。目前的抗血小板治疗对很大一部分人群仍然无效，同时存在显著的出血风险。我们探索了一种抑制动脉血栓形成的新方法。从理论上讲，通过生物物理手段，带负电荷可能会影响 vWF 的三级结构，有利于形成球状构象，而无需使用血小板失活药物。我们通过微流控血栓形成分析（MTA）实验来验证这一假设。几种不同的 CNPs 能够抑制 MTA 中的血栓形成。在小鼠中的初步研究表明，CNP 给药后血栓稳定性降低，出血时间无明显延长。这里测试的 CNPs 有望成为一类新型的抗血栓治疗药物，它们通过生物物理手段而不是生化途径发挥作用。
