Namdee Katawut, Thompson Alex J, Golinski Alexander, Mocherla Supriya, Bouis Diane, Eniola-Adefeso Omolola
Department of Biomedical Engineering, University of Michigan, 2200 Bonisteel Boulevard, 1107 C.A. Gerstacker, Ann Arbor, MI 48109, USA.
Department of Chemical Engineering, University of Michigan, 2300 Hayward Street, 3074 H. H. Dow, Ann Arbor, MI 48109, USA.
Atherosclerosis. 2014 Nov;237(1):279-86. doi: 10.1016/j.atherosclerosis.2014.09.025. Epub 2014 Sep 30.
Vascular-targeting remains a promising strategy for improving the diagnosis and treatment of coronary artery disease (CAD) by providing localized delivery of imaging and therapeutic agents to atherosclerotic lesions. In this work we evaluate how size and shape affects the capacity for a vascular-targeted carrier system to bind inflamed endothelial cells over plaque using ApoE -/- mice with developed atherosclerosis.
We investigated the adhesion levels along mouse aortae of ellipsoidal and spherical particles targeted to the inflammatory molecules E-selectin and VCAM-1, as well as the biodistribution of targeted and untargeted particles in major organs following injection via tail-vein and a 30-min circulation time.
We found that targeted ellipsoidal microparticles adhered to mouse aortae at higher levels than microspheres of similar volume, particularly at segments that contained atherosclerotic plaques. Moreover, both ellipsoidal and spherical nanoparticles displayed the same minimal adhesion levels compared to both types of microparticles evaluated, likely due to poor localization of nanoparticles to the vessel wall in blood flow. We found that microparticles targeted to plaque-associated inflammation were retained at higher levels in the lungs than untargeted particles, largely due to molecular interaction with the pulmonary endothelium. The level of the mechanical entrapment of ellipsoidal microparticles in the lungs was also not significantly different from that of microspheres of the same volume despite a ∼3-fold higher major axis length for the ellipsoids.
Particle shape and size should be considered in the design of carrier systems to target atherosclerosis, as these parameters can be tuned to improve carrier performance.
血管靶向仍然是一种很有前景的策略，通过将成像和治疗剂局部递送至动脉粥样硬化病变来改善冠状动脉疾病（CAD）的诊断和治疗。在这项研究中，我们使用患有严重动脉粥样硬化的载脂蛋白E基因敲除（ApoE-/-）小鼠，评估尺寸和形状如何影响血管靶向载体系统与斑块上炎症内皮细胞结合的能力。
我们研究了靶向炎症分子E-选择素和血管细胞黏附分子-1（VCAM-1）的椭圆形和球形颗粒沿小鼠主动脉的黏附水平，以及经尾静脉注射并经过30分钟循环时间后，靶向和非靶向颗粒在主要器官中的生物分布。
我们发现，靶向的椭圆形微粒比体积相似的微球在小鼠主动脉上的黏附水平更高，尤其是在含有动脉粥样硬化斑块的节段。此外，与所评估的两种类型的微粒相比，椭圆形和球形纳米颗粒均表现出相同的最低黏附水平，这可能是由于纳米颗粒在血流中难以定位到血管壁。我们发现，靶向斑块相关炎症的微粒在肺中的滞留水平高于非靶向微粒，这主要是由于与肺内皮细胞的分子相互作用。尽管椭圆形微粒的长轴长度约为相同体积微球的3倍，但其在肺中的机械截留水平与相同体积微球的水平也没有显著差异。
在设计靶向动脉粥样硬化的载体系统时应考虑颗粒的形状和大小，因为这些参数可以进行调整以提高载体性能。
