High-Density Branched PEGylation for Nanoparticle Drug Delivery
High-Density Branched PEGylation for Nanoparticle Drug Delivery
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DOI：
10.1007/s12195-022-00727-x
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发表时间：
2022-07-05
影响因子：
2.8
通讯作者：
Duncan, Gregg A.
中科院分区：
文献类型：
--
作者：
Cahn, Devorah;Duncan, Gregg A.
引言纳米颗粒（NP）具有致密的聚乙烯乙二醇（PEG）的表面修饰已被广泛用于改善NP循环时间，生物利用度和通过生物屏障的扩散[例如，细胞外基质（ECM），粘液]。虽然通常使用线性钉涂层，但尚未广泛探索分支的钉涂层作为NP药物输送系统的设计参数。方法NP用线性2、5、10 kDa线性钉或10 kDa星形的4臂支链钉密集地覆盖。在HEK-293T和A549细胞中评估了NP细胞摄取。使用动态光散射在24小时内在胎牛血清中评估NP稳定性。通过多个颗粒跟踪分析了NPS中NP的扩散，从囊性纤维化（CF）肺部疾病的个体中收集的痰液（粘液）扩散。与未涂层的NP相比，PEG涂层的NP在血清中看起来更稳定，但是对于分支PEG涂层的NP，吸附的总蛋白质的减少最为重要。在HEK-293T和A549细胞中，所有Pegymed NP都具有相似的细胞摄取。有趣的是，分支PEG涂层的NP具有最大的扩散系数，并且通过Matrigel移动最快。然而，在CF粘液中，线性2和5 kDa PEG涂层的NP的比例最大，而分支PEG涂层的NP与10 kDa PEG涂层的NP相比，分支PEG涂层的NP的障碍较低。结论基于通过ECM模型显着增加扩散，同时保持NP的稳定性和摄取可与线性PEG对应物相当的靶细胞，可能会提高NP效率到达目标细胞。
Introduction The surface modification of nanoparticles (NP) with a dense layer of polyethylene glycol (PEG) has been widely used to improve NP circulation time, bioavailability, and diffusion through biological barriers [e.g. extracellular matrix (ECM), mucus]. While linear PEG coatings are commonly used, branched PEG coatings have not been widely explored as a design parameter for NP drug delivery systems. Methods NPs were densely coated with either linear 2, 5, 10 kDa linear PEG or with 10 kDa star-shaped, 4-arm branched PEG. NP cellular uptake was evaluated in HEK-293T and A549 cells. NP stability was evaluated in fetal bovine serum over 24 h using dynamic light scattering. Diffusion of NPs within a Matrigel ECM model and sputum (mucus) collected from individuals with cystic fibrosis (CF) lung disease were analyzed through multiple particle tracking. Results PEG-coated NPs appeared more stable in serum compared to uncoated NPs, but the reduction in total protein adsorbed was most significant for branched PEG coated NP. All PEGylated NPs had similar cellular uptake in HEK-293T and A549 cells. Interestingly, branched-PEG coated NPs had the largest diffusion coefficient and moved most rapidly through Matrigel. However in CF mucus, linear 2 and 5 kDa PEG coated NPs had the largest fraction of rapidly diffusing particles while branched PEG coated NPs had less hindered mobility compared to linear 10 kDa PEG coated NPs. Conclusion Branched PEGylation may have the potential to increase NP efficiency in reaching target cells based on an apparent increase in diffusion through an ECM model while maintaining NP stability and uptake in target cells comparable to their linear PEG counterparts.