This work reports an innovative and very effective gene delivery nanosystem, based on the combination of poly[(2-dimethylamino)ethyl methacrylate] (PDMAEMA) and poly(β-amino ester) (PβAE) homopolymers, that has the capacity to efficiently deliver genetic material into target cells, even in the presence of serum. The best formulation, prepared with the combination PDMAEMA/4PβAE at the 25/1 nitrogen/phosphate (N/P) ratio, presented a 700-fold and 220-fold higher transfection activity than that obtained with branched polyethylenimine (PEI)-based polyplexes and block copolymer-based polyplexes, respectively. This new nanocarrier revealed high transgene expression in different human cells, including hard-to-transfect normal human astrocytes. The polyplexes presented high protection of genetic material and reduced sizes, which are suitable physicochemical properties for in vivo applications. Overall, this study demonstrates that the combination of PDMAEMA and PβAE homopolymers resulted in a noticeable and synergistic effect in terms of transfection activity, without causing substantial toxicity, constituting a new platform for the development of gene delivery nanosystems.

中文翻译：

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聚[（甲基丙烯酸2-（2-二甲基氨基）乙酯]和聚（β-氨基酯）的结合产生强而协同的转染活性

这项工作报告了一种创新且非常有效的基因传递纳米系统，该系统基于聚[（甲基丙烯酸2-（二甲基氨基）乙基酯]（PDMAEMA）和聚（β-氨基酯）（PβAE）均聚物的组合）即使存在血清，遗传物质也可进入靶细胞。以25/1氮/磷酸盐（N / P）的比例结合PDMAEMA /4PβAE制备的最佳配方，其转染活性比基于支链聚乙烯亚胺（PEI）的复合物获得的转染活性高700倍和220倍和基于嵌段共聚物的复合物。这种新的纳米载体揭示了在不同人类细胞（包括难以转染的正常人类星形胶质细胞）中的高转基因表达。多链体对遗传物质具有高度保护作用，并且尺寸减小，对于体内应用而言，它们是合适的物理化学性质。总体而言，这项研究表明，PDMAEMA和PβAE均聚物的组合在转染活性方面产生了显着且协同的作用，而没有引起实质性的毒性，为基因传递纳米系统的开发提供了新的平台。