Polysaccharide-oligoamine based conjugates for gene delivery
Polysaccharide-oligoamine based conjugates for gene delivery
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DOI：
10.1021/jm0105528
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发表时间：
2002-04-25
影响因子：
7.3
通讯作者：
Domb, AJ
中科院分区：
文献类型：
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作者：
Azzam, T;Eliyahu, H;Domb, AJ
这项工作描述了一种多功能和通用的聚阳离子系统的基础上，寡胺接枝在天然多糖，能够复合各种质粒和管理它们到各种细胞在高产率，以产生所需的蛋白质。预期这些聚阳离子更好地满足质粒或反义的有效复合和递送的要求，并且以受控速率生物降解成无毒组分。所开发的生物可降解聚阳离子是基于精胺，一种天然四胺，与葡聚糖或阿拉伯半乳聚糖缀合。这些聚阳离子通过氧化多糖与所需的低聚胺的还原胺化制备。用硼氢化钠将得到的席夫碱共轭物还原为稳定的胺共轭物。超过300种不同的聚阳离子从各种多糖和低聚胺开始制备，主要是2至4个氨基的低聚胺。虽然大多数这些共轭物形成稳定的复合物与各种质粒的浊度实验确定，只有少数聚阳离子被发现是积极的，在pancreecting细胞。这项工作表明聚阳离子的结构在聚阳离子的转染活性中起着重要的作用。
This work describes a versatile and universal polycation system based on oligoamines grafted on natural polysaccharides that is capable of complexing various plasmids and administering them into various cells in high yield to produce a desired protein. These polycations are expected to better meet the requirements for effective complexation and delivery of plasmid or an antisense and to biodegrade into nontoxic components at a controlled rate. The developed biodegradable polycations are based on spermine, a natural tetramine, conjugated to dextran or arabinogalactan. These polycations were prepared by reductive amination of oxidized polysaccharides with the desired oligoamines. The Schiff base conjugates thus obtained were reduced to the stable amine conjugates by sodium borohydride. Over 300 different polycations were prepared starting from various polysaccharides and oligoamines, mainly oligoamines of two to four amino groups. Although most of these conjugates formed stable complexes with various plasmids as determined by turbidity experiments, only a few polycations were found to be active in transfecting cells. This work indicates that the structure of the polycation plays a significant role in the transfection activity of polycations.