Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, United States.
Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, United States; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, United States.
Acta Biomater. 2015 Jul;21:99-108. doi: 10.1016/j.actbio.2015.04.005. Epub 2015 Apr 11.
For vascular-targeting carrier (VTC) systems to be effective, carriers must be able to localize and adhere to the vascular wall at the target site. Research suggests that neutrally buoyant nanoparticles are limited by their inability to localize to the endothelium, making them sub-optimal as carriers. This study examines whether particle density can be exploited to improve the targeting (localization and adhesion) efficiency of nanospheres to the vasculature. Silica spheres with 500 nm diameter, which have a density roughly twice that of blood, exhibit improved adhesion to inflamed endothelium in an in vitro model of human vasculature compared to neutrally buoyant polystyrene spheres of the same size. Silica spheres also display better near-wall localization in the presence of red blood cells than they do in pure buffer, likely resulting in the observed improvement in adhesion. Titania spheres (4 times more dense than blood) adhere at levels higher than polystyrene, but only in conditions when gravity or centrifugal force acts in the direction of adhesion. In light of the wide array of materials proposed for use as carrier systems for drug delivery and diagnostics, particle density may be a useful tool for improving the targeting of diseased tissues.
为了使血管靶向载体(VTC)系统有效,载体必须能够在靶部位定位并黏附于血管壁。研究表明,中性浮力纳米颗粒由于无法定位于内皮细胞,因此作为载体的效果并不理想。本研究探讨了是否可以利用颗粒密度来提高纳米球对血管的靶向(定位和黏附)效率。与大小相同的中性浮力聚苯乙烯纳米球相比,直径为 500nm 的二氧化硅纳米球密度约为血液的两倍,在体外人类血管模型中表现出对炎症内皮的黏附能力增强。与纯缓冲液相比,二氧化硅纳米球在存在红细胞的情况下具有更好的近壁定位,这可能导致观察到的黏附能力增强。氧化钛纳米球(密度是血液的四倍)黏附的水平高于聚苯乙烯,但仅在重力或离心力沿黏附方向作用的情况下。鉴于广泛提出的各种材料可用于药物输送和诊断的载体系统,颗粒密度可能是提高疾病组织靶向性的有用工具。