Relationship between complement activation, cellular uptake and surface physicochemical aspects of novel PEG-modified nanocapsules
Relationship between complement activation, cellular uptake and surface physicochemical aspects of novel PEG-modified nanocapsules
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DOI：
10.1016/s0142-9612(01)00043-6
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发表时间：
2001-11-01
期刊：
影响因子：
14
通讯作者：
Barratt, G
中科院分区：
文献类型：
--
作者：
Mosqueira, VCF;Legrand, P;Barratt, G
我们工作的目的是研究通过吸附或共价接枝聚环氧乙烷（PEG）对纳米胶囊（NC）表面进行修饰，以及其磷脂（PL）含量的变化对补体激活（C3裂解）和巨噬细胞摄取的影响。对纳米胶囊的物理化学特性描述包括对其性质的研究，例如表面电荷、大小、亲水性、形态和均一性。这是首次将此类性质与纳米胶囊的生物相互作用相关联，纳米胶囊是一种结构比纳米球更复杂的新型载体系统。C3交叉免疫电泳显示，具有较长PEG链和较高密度的纳米胶囊的激活作用降低，尽管所有配方都或多或少地诱导了C3裂解。表面共价结合PEG的纳米胶囊比普通聚乳酸[聚（D,L - 丙交酯）]纳米胶囊或纳米球（NS）对补体的激活作用更弱。此外，与纳米胶囊接触的J774A1细胞的荧光/共聚焦显微镜观察显示，与带有PEG的纳米胶囊的相互作用显著降低。然而，PEG的连接方式（共价或吸附）似乎影响摄取机制。综上所述，这些结果表明，蛋白质与覆盖有高密度20 kDa PEG链的纳米胶囊的低结合水平可能是由于这些颗粒周围的空间位阻，它阻止了蛋白质吸附并减少了它们与巨噬细胞的相互作用。（C）2001爱思唯尔科学有限公司。保留所有权利。
The aim of our work was to examine the relationship between modifications of the surface of nanocapsules (NC) by adsorption or covalent grafting of poly(ethylene oxide) (PEG), and changes in their phospholipid (PL) content on complement activation (C3 cleavage) and on uptake by macrophages. The physicochemical characterization of the NC included an investigation of their properties, such as surface charge, size, hydrophilicity, morphology and homogeneity. This is the first time that such properties have been correlated with biological interactions for NC, a novel carrier system with a structure more complex than nanospheres. C3 crossed immunoelectrophoresis revealed the reduced activation for NC with longer PEG chain and higher density, although all formulations induced C3 cleavage to a lesser or greater extent. NC bearing PEG covalently bound to the surface were weaker activators of complement than plain PLA [poly(D,L-lactide)] NC or nanospheres (NS). Furthermore, the fluorescent/confocal microscopy of J774A1 cells in contact with NC reveal a dramatically reduced interaction with PEG-bearing NC However, the way in which PEG was attached (covalent or adsorbed) seemed to affect the mechanism of uptake. Taken together, these results suggest that the low level of protein binding to NC covered with a high density of 20 kDa PEG chains is likely to be due to the steric barriers surrounding these particles, which prevents protein adsorption and reduces their interaction with macrophages. (C) 2001 Elsevier Science Ltd. All rights reserved.