The effect of poly(ethylene glycol) molecular architecture on cellular interaction and uptake of DNA complexes
The effect of poly(ethylene glycol) molecular architecture on cellular interaction and uptake of DNA complexes
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DOI：
10.1016/j.jconrel.2004.02.019
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发表时间：
2004-05-31
影响因子：
10.8
通讯作者：
Stolnik, S
中科院分区：
文献类型：
--
作者：
Deshpande, MC;Davies, MC;Stolnik, S
使用流式细胞荧光法和激光共聚焦显微镜研究了质粒 DNA 复合物与一系列具有不同结构的叔胺甲基丙烯酸酯-乙二醇 (DMAEMA-EG) 共聚物的细胞摄取。根据共聚物分子结构，复合物表现出不同的细胞相互作用和内化速率和程度。一般来说，寡聚乙二醇[OEG]或聚乙二醇[PEG]链的引入降低了DNA复合物的相互作用和细胞内化，但观察到了细微的差异。两种嵌段共聚物，即“瓶刷”型 DMAEMA-嵌段-OEGMA 和线性 DMAEMA-嵌段-PEG 共聚物（每种共包含 45 个 EG 单元），显示出相似的吸收曲线。相比之下，尽管每个 PEG 链包含 45 个 EG 单元，但仅观察到由梳型统计共聚物 DMAEMA-stat-PEGMA 形成的复合物的吸收相对较低。在 A549、HepG2 和 COS-7 三种细胞系中观察到类似的趋势。然而，绝对值是细胞依赖性的，COS-7 细胞显示出最高的摄取率和程度。对复合物的缔合和吸收的研究表明，细胞缔合通常随着时间的推移而增加，吸收水平和时间分布取决于聚合物结构。共聚焦显微镜研究证实，除了转染效果差的梳型共聚物外，复合物与细胞的结合导致了内吞作用。 (C) 2004 Elsevier B.V. 保留所有权利。
The cellular uptake of plasmid DNA complexes with a series of tertiary amine methacrylate-ethylene glycol (DMAEMA-EG) copolymers with various architectures was studied using flow cytofluorometry and laser confocal microscopy. The complexes displayed different rates and extents of cellular interaction and internalisation, depending on the copolymer molecular architecture. In general, introduction of oligo(ethylene glycol) [OEG] or poly(ethylene glycol) [PEG] chains decreased both the interaction and cellular internalisation of the DNA complexes but subtle differences were observed. Two block copolymers, a 'bottle-brush' type DMAEMA-block-OEGMA and a linear DMAEMA-block-PEG copolymer (each containing a total of 45 EG units), displayed similar uptake profiles. In contrast, only relatively low uptake of complexes formed by a comb-type statistical copolymer, DMAEMA-stat-PEGMA, was observed, despite each PEG chain comprising 45 EG units. Similar trends were observed with three cell lines, A549, HepG2 and COS-7. However, the absolute values were cell-dependent, with COS-7 cells displaying both the highest rate and extent of uptake. Studies of the association and uptake of the complexes demonstrated that cell associations generally increased over time, with the uptake level and the time profile depending on the polymer architecture. Confocal microscopy studies confirmed that, with the exception of the poorly transfecting comb-type copolymer, the association of complexes with cells resulted in endocytosis. (C) 2004 Elsevier B.V. All rights reserved.