Gene carriers based on hexanediol diacrylate linked oligoethylenimine: Effect of chemical structure of polymer on biological properties
Gene carriers based on hexanediol diacrylate linked oligoethylenimine: Effect of chemical structure of polymer on biological properties
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DOI：
10.1021/bc060133v
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发表时间：
2006-09-20
影响因子：
4.7
通讯作者：
Wagner, Ernst
中科院分区：
文献类型：
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作者：
Kloeckner, Julia;Bruzzano, Stefano;Wagner, Ernst
采用20℃(LT-OEI-HD)和60℃(HT-OEI-HD)两种不同的反应温度，合成了两种基于己二醇二丙烯酸酯连接的低乙烯基亚胺(OEI)的可生物降解聚阳离子。用核磁共振、傅里叶变换红外光谱和SEC/MALLS(尺寸排除层析多角度激光光散射检测)对其结构进行了分析。反应温度强烈影响聚合物的相对分子质量和酯/酰胺比，从而导致聚阳离子具有不同的生物活性和降解性。LT-OEIHD是一种8.7 kDa的酯基聚阳离子，分别在pH=7和pH=9时迅速降解。HT-OEI-HD的相对分子质量为26.6 kDa，主要以酰胺类化合物为主，降解速度较LT-OEIHD慢。这两种聚合物在两种细胞系中的基因转移效率与22 kDa的线性聚乙烯亚胺一样有效，同时在其最佳偶联/质粒(C/P)比例下毒性较小。LT-OEI-HD需要更高的C/P比率来进行基因传递；然而，它的毒性明显低于HT-OEI-HD。
Two biodegradable polycations based on hexanediol diacrylate linked oligoethylenimine (OEI) were synthesized by applying different reaction temperatures, 20 degrees C (LT-OEI-HD) and 60 degrees C (HT-OEI-HD). Their structural properties were analyzed by NMR, FTIR, and SEC/MALLS ( size exclusion chromatography coupled with multiangle laser light scattering detection). Reaction temperature strongly influenced molecular weight and ester/amide ratio and thus resulted in polycations with different biological activities and degradation profiles. LT-OEIHD was an ester-based polycation of 8.7 kDa which degraded rapidly at pH 7 and pH 9 respectively. HT-OEI-HD had a molecular weight of 26.6 kDa, was mainly based on amides, and degraded more slowly than LT-OEIHD. Both polymers mediated gene transfer as efficiently as linear polyethylenimine of 22 kDa in two cell lines while being less toxic at their optimal conjugate/plasmid (C/P) ratios. LT-OEI-HD needed higher C/P ratios for gene delivery; however, it was significantly less toxic than HT-OEI-HD.