新型聚乙二醇化聚天冬酰胺类超分子聚合物基因载体的研究
New pegylated polyaspartamide-based polyplexes as gene delivery vectors.
机构信息
Laboratory of Biocompatible Polymers, Department Chimicae Tecnologie Farmaceutiche, University of Palermo, Via Archirafi, 32, 90123 Palermo, Italy.
出版信息
Nanomedicine (Lond). 2010 Feb;5(2):243-58. doi: 10.2217/nnm.09.104.
AIMS
To synthesize novel polyhydroxyethylaspartamide (PHEA) copolymers containing spermine (Spm) and polyethylene glycol (PEG) moieties in high yields, with the expectation that this material would show stealth properties and the ability to complex DNA by electrostatic interactions.
MATERIALS & METHODS: PHEA-PEG-Spm copolymer was prepared with a two-step reaction. Chemical, physicochemical and biological characterizations of PHEA-PEG-Spm copolymers and their obtained polyplexes with pDNA were performed.
RESULTS
The introduction of spermine in PHEA structure allows to obtain a copolymer bearing in the side chains polyamine moieties capable to interact with DNA. On the other hand, the introduction of PEG in polymeric structure increased the DNA condensing ability of PHEA-PEG-Spm copolymer in comparison with the derivatives without PEG (PHEA-Spm), and improved its characteristics of biocompatibility.
CONCLUSIONS
PHEA-PEG-Spm copolymer shows excellent ability to complex and condense plasmidic DNA giving interpolyelectrolyte complexes to act as gene delivery systems. Moreover, PEGylation confers to the obtained interpolyelectrolyte complexes stealth properties.
目的
以高产率合成新型聚羟乙基天冬酰胺（PHEA）共聚物，其中含有精胺（Spm）和聚乙二醇（PEG）部分，期望该材料具有隐形特性和通过静电相互作用与 DNA 复合的能力。
材料与方法
通过两步反应制备 PHEA-PEG-Spm 共聚物。对 PHEA-PEG-Spm 共聚物及其与 pDNA 形成的聚阳离子复合物进行了化学、物理化学和生物学表征。
结果
在 PHEA 结构中引入精胺可得到在侧链上带有聚胺部分的共聚物，这些聚胺部分能够与 DNA 相互作用。另一方面，在聚合物结构中引入 PEG 可提高 PHEA-PEG-Spm 共聚物与不含 PEG（PHEA-Spm）的衍生物相比，DNA 凝聚能力，并改善其生物相容性。
结论
PHEA-PEG-Spm 共聚物具有极好的与质粒 DNA 复合和凝聚能力，形成聚电解质复合物作为基因传递系统。此外，PEG 化赋予了所得聚电解质复合物隐形特性。
Zotero 插件