Regulating the surface poly(ethylene glycol) density of polymeric nanoparticles and evaluating its role in drug delivery in vivo
Regulating the surface poly(ethylene glycol) density of polymeric nanoparticles and evaluating its role in drug delivery in vivo
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DOI：
10.1016/j.biomaterials.2015.07.048
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发表时间：
2015-11-01
期刊：
影响因子：
14
通讯作者：
Wang, Jun
中科院分区：
文献类型：
--
作者：
Du, Xiao-Jiao;Wang, Ji-Long;Wang, Jun
聚乙二醇(PEG)通常被用来保护纳米颗粒在血液中的快速清除。这种影响高度依赖于纳米颗粒的表面聚乙二醇组分密度。然而，由于在保持其他纳米性质的同时精确控制表面聚乙二醇密度的关键技术，在聚乙二醇密度和体内给药方面缺乏详细和翔实的研究。在纳米粒子的制备过程中，我们通过将聚(E-己内酯)(PCL)均聚物引入到聚乙二醇嵌段聚(E-己内酯)(PEGPCL)中，并调整PCL与PEGPCL的质量比来调节聚合物纳米粒子的尺寸和表面聚乙二醇酯的密度。我们通过改变聚乙二醇-聚乙二醇单嵌段的相对分子质量和调节聚乙二醇单分子重复单元的摩尔比(CL)和聚乙二醇单环(EG)的摩尔比，进一步开发了具有不同但可控制的尺寸和表面聚乙二醇密度的聚合物纳米粒子的库。从而获得了一组表面聚乙二醇组分密度不同但其他纳米性质相同的纳米粒子，并考察了表面聚乙二醇组分密度对纳米粒子在小鼠体内生物学行为的影响。我们发现，较高的表面聚乙二醇组分密度使得纳米粒子抵抗血清蛋白的吸收和巨噬细胞的摄取，导致纳米粒子在肿瘤组织中积累更多，从而弥补了肿瘤细胞内化减少的缺陷，从而在携带多西紫杉醇时具有优越的抗肿瘤效果。(C)2015爱思唯尔有限公司。保留所有权利。
Poly(ethylene glycol) (PEG) is usually used to protect nanoparticles from rapid clearance in blood. The effects are highly dependent on the surface PEG density of nanoparticles. However, there lacks a detailed and informative study in PEG density and in vivo drug delivery due to the critical techniques to precisely control the surface PEG density when maintaining other nano-properties. Here, we regulated the polymeric nanoparticles' size and surface PEG density by incorporating poly(E-caprolactone) (PCL) homopolymer into poly(ethylene glycol)-block-poly(E-caprolactone) (PEG-PCL) and adjusting the mass ratio of PCL to PEG-PCL during the nanoparticles preparation. We further developed a library of polymeric nanoparticles with different but controllable sizes and surface PEG densities by changing the molecular weight of the PCL block in PEG-PCL and tuning the molar ratio of repeating units of PCL (CL) to that of PEG (EG). We thus obtained a group of nanoparticles with variable surface PEG densities but with other nano-properties identical, and investigated the effects of surface PEG densities on the biological behaviors of nanoparticles in mice. We found that, high surface PEG density made the nanoparticles resistant to absorption of serum protein and uptake by macrophages, leading to a greater accumulation of nanoparticles in tumor tissue, which recuperated the defects of decreased internalization by tumor cells, resulting in superior antitumor efficacy when carrying docetaxel. (C) 2015 Elsevier Ltd. All rights reserved.