Local inflammation of the endothelium is associated with a plethora of cardiovascular diseases. Vascular‐targeted carriers (VTCs) have been advocated to provide focal effective therapeutics to these disease sites. Here, we examine the design of functionalized nanoparticles (NPs) as VTCs that can specifically localize at an inflamed vessel wall under pathological levels of high shear stress, associated for example with clinical (or in vivo) conditions of vascular narrowing and arteriogenesis. To test this, carboxylated fluorescent 200 nm polystyrene particles were functionalized with ligands to activated endothelium, that is, an E‐selectin binding peptide (Esbp), an anti ICAM‐1 antibody, or using a combination of both. The functionalized NPs were investigated in vitro using microfluidic models lined with inflamed (TNF‐α stimulated) and control endothelial cells (EC). Specifically, their adhesion was monitored under different relevant wall shear stresses (i.e., 40–300 dyne/cm²) via real‐time confocal microscopy. Experiments reveal a significantly higher specific adhesion of the examined functionalized NPs to activated EC for the window of examined wall shear stresses. Moreover, particle adhesion correlated with the surface coating density whereby under high surface coating (i.e., ~10,000 molecule/particle), shear‐dependent particle adhesion increased significantly. Altogether, our results show that functionalized NPs can be designed to target inflamed endothelial cells under high shear stress. Such VTCs underscore the potential for attractive avenues in targeting drugs to vasoconstriction and arteriogenesis sites.

中文翻译：

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在高壁剪切应力下将功能化的纳米粒子靶向活化的内皮细胞。

内皮的局部炎症与多种心血管疾病有关。有人提倡以血管为靶标的载体（VTC）为这些疾病部位提供集中有效的治疗方法。在这里，我们检查了功能化的纳米颗粒（NPs）作为VTC的设计，这些VTC可以在高剪切应力的病理水平（例如与血管狭窄和动脉生成的临床（或体内）状况相关）下特异性地定位在发炎的血管壁上。为了对此进行测试，将羧基化的200 nm荧光聚苯乙烯颗粒用配体功能化到活化的内皮，即E-选择蛋白结合肽（Esbp），抗ICAM-1抗体或两者结合使用。使用内衬发炎（TNF-α刺激）和对照内皮细胞（EC）的微流模型体外研究了功能化的NP。具体而言，在不同的相关壁切应力（即40–300达因/厘米）下监测它们的附着力²）通过实时共聚焦显微镜检查。实验显示，对于所检查的壁切应力窗口，所检查的官能化NP与活化的EC的比粘附力明显更高。此外，颗粒的附着力与表面涂层的密度相关，因此在高表面涂层（即约10,000个分子/颗粒）下，剪切相关的颗粒的附着力显着增加。总而言之，我们的结果表明，可以将功能化的NP设计为在高剪切应力下靶向发炎的内皮细胞。此类VTC强调了将药物靶向血管收缩和动脉生成部位的诱人途径的潜力。