High-Density Branched PEGylation for Nanoparticle Drug Delivery.

IF 2.3 4区医学 Q3 BIOPHYSICS Cellular and molecular bioengineering Pub Date : 2022-10-01 DOI:10.1007/s12195-022-00727-x

Devorah Cahn, Gregg A Duncan

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引用次数: 1

Abstract

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.

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高密度支链聚乙二醇化用于纳米颗粒药物递送。

用聚乙二醇(PEG)致密层对纳米颗粒(NP)进行表面修饰已被广泛用于改善NP的循环时间、生物利用度和通过生物屏障(如细胞外基质(ECM)、粘液)的扩散。虽然线性PEG涂层通常被使用，但分枝PEG涂层尚未被广泛探索作为NP给药系统的设计参数。方法:用2、5、10 kDa线性聚乙二醇或10 kDa星形四臂支链聚乙二醇包覆NPs。在HEK-293T和A549细胞中评估NP细胞摄取。采用动态光散射法评价胎牛血清中NP的稳定性。通过多粒子跟踪分析NPs在Matrigel ECM模型和囊性纤维化(CF)肺部疾病患者的痰(粘液)中的扩散。结果:与未包被的NP相比，PEG包被的NP在血清中表现出更稳定的状态，但支链PEG包被的NP吸附总蛋白的减少最为显著。所有聚乙二醇化的NPs在HEK-293T和A549细胞中具有相似的细胞摄取。有趣的是，支链peg涂层的NPs具有最大的扩散系数，并且在矩阵中移动最快。然而，在CF黏液中，线性2和5 kDa PEG包被的NPs具有最大比例的快速扩散颗粒，而与线性10 kDa PEG包被的NPs相比，支链PEG包被的NPs具有更少的迁移障碍。结论:通过ECM模型，支链聚乙二醇化可能有可能提高NP到达靶细胞的效率，这是基于扩散的明显增加，同时保持NP在靶细胞中的稳定性和摄取，与线性聚乙二醇化相当。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular and molecular bioengineering 生物-生物物理

CiteScore

5.60

自引率

3.60%

发文量

审稿时长

>12 weeks

期刊介绍： The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas: Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example. Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions. Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress. Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.