Network of Excellence for Functional Biomaterials, NFB Building, IDA Business Park, Newcastle Road, Dangan, National University of Ireland, Galway, Ireland.
Int J Pharm. 2012 Sep 15;434(1-2):99-105. doi: 10.1016/j.ijpharm.2012.05.010. Epub 2012 Jun 2.
A unique hyperbranched polymeric system with a linear poly-2-dimethylaminoethyl methacrylate (pDMAEMA) block and a hyperbranched polyethylene glycol methyl ether methacrylate (PEGMEMA) and ethylene dimethacrylate (EGDMA) block was designed and synthesized via deactivation enhanced atom transfer radical polymerisation (DE-ATRP) for efficient gene delivery. Using this unique structure, with a linear pDMAEMA block, which efficiently binds to plasmid DNA (pDNA) and hyperbranched polyethylene glycol (PEG) based block as a protective shell, we were able to maintain high transfection levels without sacrificing cellular viability even at high doses. The transfection capability and cytotoxicity of the polymers over a range of pDNA concentration were analysed and the results were compared to commercially available transfection vectors such as polyethylene imine (branched PEI, 25 kDa), partially degraded poly(amido amine)dendrimer (dPAMAM; commercial name: SuperFect(®)) in fibroblasts and adipose tissue derived stem cells (ADSCs).
设计并合成了一种独特的超支化聚合物体系，该体系具有线性聚 2-二甲氨基乙基甲基丙烯酸酯（pDMAEMA）嵌段和超支化聚乙二醇甲基醚甲基丙烯酸酯（PEGMEMA）和二乙二醇二甲基丙烯酸酯（EGDMA）嵌段，通过失活增强原子转移自由基聚合（DE-ATRP）用于高效基因传递。利用这种独特的结构，带有线性 pDMAEMA 嵌段，可有效地与质粒 DNA（pDNA）结合，而超支化聚乙二醇（PEG）作为保护壳，即使在高剂量下，我们也能够保持高转染水平而不牺牲细胞活力。分析了聚合物在一系列 pDNA 浓度下的转染能力和细胞毒性，并将结果与商业上可获得的转染载体（如聚乙烯亚胺（支化 PEI，25 kDa）、部分降解的聚酰胺胺树枝状大分子（dPAMAM；商品名：SuperFect（®）））进行比较，在成纤维细胞和脂肪组织来源的干细胞（ADSCs）中进行比较。
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