Gene transfection with polymeric carrier remains a challenge; particularly, high transfection levels combined with low toxicity are hard to achieve. We herein revisit polyvinylamines, an old and neglected family of cationic polymers. They can be readily obtained by controlled hydrolysis of polyvinylamides prepared through (controlled) radical polymerization. A series of tailor-made and well-defined polyvinylamines bearing primary amino groups, and poly(N-methylvinylamine) bearing secondary amines, were evaluated for the transfection of cells with pDNA as a function of their molar mass, molar mass distribution, and degree of deacetylation. Unexpected high transfection levels, in combination with low cytotoxicity were recorded for both series. Surprisingly, a great impact of the molar mass was observed for the primary amine polyvinylamine series, whereas the results were mostly independent of molar mass or dispersity for the polymer bearing secondary amine. It was further established that a certain percentage of acetamide groups increased the transfection level, while maintaining low cytotoxicity. These results highlight for the first time the real potential of polyvinylamines as gene carriers, and make these polymers very attractive for further development in gene therapy.

译文

用聚合物载体进行基因转染仍然是一个挑战; 特别是,很难实现高转染水平和低毒性。我们在此重新审视聚乙烯胺,这是一种古老而被忽视的阳离子聚合物家族。通过 (受控) 自由基聚合制备的聚乙烯酰胺的受控水解,可以很容易地获得它们。评估了一系列量身定制的,定义明确的带有伯氨基的聚乙烯胺和带有仲胺的聚 (N-甲基乙烯基胺),用于用pDNA转染细胞,其摩尔质量,摩尔质量分布和脱乙酰化程度。这两个系列都记录了意外的高转染水平和低细胞毒性。令人惊讶的是,观察到伯胺聚乙烯胺系列的摩尔质量有很大的影响,而结果与带有仲胺的聚合物的摩尔质量或分散性无关。进一步确定,一定百分比的乙酰胺基团增加了转染水平,同时保持了较低的细胞毒性。这些结果首次突出了聚乙烯胺作为基因载体的真正潜力,并使这些聚合物对基因治疗的进一步发展非常有吸引力。

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