Dense and Dynamic Polyethylene Glycol Shells Cloak Nanoparticles from Uptake by Liver Endothelial Cells for Long Blood Circulation.
Dense and Dynamic Polyethylene Glycol Shells Cloak Nanoparticles from Uptake by Liver Endothelial Cells for Long Blood Circulation.
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DOI：
10.1021/acsnano.8b04947
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发表时间：
2018-10-23
期刊：
影响因子：
17.1
通讯作者：
Cheng H
中科院分区：
文献类型：
--
作者：
Zhou H;Fan Z;Li PY;Deng J;Arhontoulis DC;Li CY;Bowne WB;Cheng H
对长循环纳米粒子的研究过去一直集中在减少巨噬细胞对它们的清除上。通过在纳米颗粒表面设计一种层次化的聚乙二醇(PEG)结构，我们揭示了增强纳米颗粒血液循环的另一种机制。在传统的聚乙二醇化纳米颗粒上以接近但低于蘑菇到刷子过渡区域的密度连接第二层聚乙二醇酯，通过减少肝脏中非库普弗细胞，特别是肝窦内皮细胞(LSECs)对纳米颗粒的摄取，显著延长了它们的血液循环。我们的研究还发现，动态的外层聚乙二醇层降低了蛋白质与纳米颗粒的结合亲和力，尽管不会减少吸附的蛋白质总数。外层聚乙二醇层的这些影响在较高密度区减弱。因此，我们的结果表明，纳米粒子的动态形貌结构是决定其在体内命运的重要因素。综上所述，这项研究增进了我们对纳米颗粒血液循环的理解，并为制备长循环纳米颗粒提供了一种简便的方法。
Research into long-circulating nanoparticles has in the past focused on reducing their clearance by macrophages. By engineering a hierarchical polyethylene glycol (PEG) structure on nanoparticle surfaces, we revealed an alternative mechanism to enhance nanoparticle blood circulation. The conjugation of a second PEG layer at a density close to, but lower than the mushroom-to-brush transition regime on conventional PEGylated nanoparticles dramatically prolongs their blood circulation via reduced nanoparticle uptake by non-Kupffer cells in the liver, especially liver sinusoidal endothelial cells (LSECs). Our study also disclosed that the dynamic outer PEG layer reduces protein binding affinity to nanoparticles, although not the total number of adsorbed proteins. These effects of the outer PEG layer diminishes in the higher density regime. Therefore, our results suggest that the dynamic topographical structure of nanoparticles is an important factor in governing their fate in vivo. Taken together, this study advances our understanding of nanoparticle blood circulation and provides a facile approach for generating long circulating nanoparticles.
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