Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
J Cardiovasc Transl Res. 2013 Aug;6(4):570-8. doi: 10.1007/s12265-013-9460-5. Epub 2013 May 3.
Endothelial cell (EC) activation and inflammation is a key step in the initiation and progression of many cardiovascular diseases. Targeted delivery of therapeutic reagents to inflamed EC using nanoparticles is challenging as nanoparticles do not arrest on EC efficiently under high shear stress. In this study, we developed a novel polymeric platelet-mimicking nanoparticle for strong particle adhesion onto ECs and enhanced particle internalization by ECs. This nanoparticle was encapsulated with dexamethasone as the anti-inflammatory drug, and conjugated with polyethylene glycol, glycoprotein 1b, and trans-activating transcriptional peptide. The multi-ligand nanoparticle showed significantly greater adhesion on P-selectin, von Willebrand Factor, than the unmodified particles, and activated EC in vitro under both static and flow conditions. Treatment of injured rat carotid arteries with these multi-ligand nanoparticles suppressed neointimal stenosis more than unconjugated nanoparticles did. These results indicate that this novel multi-ligand nanoparticle is efficient to target inflamed EC and inhibit inflammation and subsequent stenosis.
内皮细胞（EC）激活和炎症是许多心血管疾病发生和发展的关键步骤。使用纳米颗粒将治疗试剂靶向递送至炎症 EC 具有挑战性，因为纳米颗粒在高剪切应力下不能有效地在内皮细胞上停留。在这项研究中，我们开发了一种新型聚合物血小板模拟纳米颗粒，用于将颗粒强烈粘附到 EC 上，并增强 EC 对颗粒的内化。该纳米颗粒包封有地塞米松作为抗炎药物，并与聚乙二醇、糖蛋白 1b 和反式激活转录肽结合。与未修饰的颗粒相比，多配体纳米颗粒在 P-选择素、血管性血友病因子上的粘附明显更强，并且在静态和流动条件下均可在体外激活 EC。用这些多配体纳米颗粒处理受伤的大鼠颈动脉可抑制新生内膜狭窄，效果优于未结合的纳米颗粒。这些结果表明，这种新型多配体纳米颗粒能够有效地靶向炎症 EC 并抑制炎症和随后的狭窄。
