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首页> 外文期刊>Biomaterials >The effect of polymer architecture, composition, and molecular weight on the properties of glycopolymer-based non-viral gene delivery systems.
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The effect of polymer architecture, composition, and molecular weight on the properties of glycopolymer-based non-viral gene delivery systems.

机译：聚合物结构，组成和分子量对基于糖聚合物的非病毒基因递送系统特性的影响。

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Although a variety of non-viral gene delivery vectors has been synthesized and used for gene delivery purposes, well-defined glycopolymer-based gene delivery carriers is not well explored. Reversible Addition-Fragmentation Chain Transfer (RAFT) polymerization technique allows successful and facile synthesis of cationic glycopolymers containing pendant sugar moieties in the absence of protecting group chemistry. A library of cationic glycopolymers of pre-determined molar masses and narrow polydispersities ranging from 3 to 30 kDa has been synthesized using RAFT polymerization technique. These polymers differ from each other in their architectures (block versus random), molecular weights, and monomer ratios (carbohydrate to cationic segment). It is shown that the above-mentioned parameters can largely affect the toxicity, DNA condensation ability and gene delivery efficacy of these polymers. Statistical copolymers of high degree of polymerization are found to be the ideal vector for gene delivery purposes. These statistical copolymers show lower toxicity and higher gene expression in the presence and absence of serum, as compared to the corresponding diblock copolymers. This is the first example of well-defined synthetic glycopolymers as DNA carriers that works both in the presence and absence of serum proteins. The critical composition of carbohydrate segment in copolymers for enhanced gene delivery and low toxicity was determined and an increase in carbohydrate residues in copolymers resulted in a decrease in transfection efficiencies of these polymers. The effect of serum proteins on statistical and diblock copolymer based polyplexes and hence gene delivery efficacy was studied. The results showed that the diblock copolymer-based polyplexes showed lower interactions with serum proteins, lower cellular uptake and very low gene expression in both Hep G2 and Hela cells in comparison to statistical copolymers.
机译：尽管已经合成了多种非病毒基因递送载体并将其用于基因递送目的，但是尚未很好地探索基于定义明确的基于糖聚合物的基因递送载体。可逆的加成-断裂链转移（RAFT）聚合技术可在没有保护基化学的情况下成功且轻松地合成包含侧链糖部分的阳离子糖聚合物。已使用RAFT聚合技术合成了具有预定摩尔质量和3-30 kDa的窄多分散性的阳离子糖聚合物库。这些聚合物的结构（嵌段与无规），分子量和单体比率（碳水化合物与阳离子链段）互不相同。结果表明，上述参数可以极大地影响这些聚合物的毒性，DNA缩合能力和基因传递功效。发现高聚合度的统计共聚物是用于基因递送目的的理想载体。与相应的二嵌段共聚物相比，这些统计共聚物在存在和不存在血清的情况下显示出较低的毒性和较高的基因表达。这是定义明确的合成糖聚合物作为DNA载体的第一个例子，它可以在存在或不存在血清蛋白的情况下起作用。确定了用于提高基因递送和低毒性的共聚物中碳水化合物链段的关键组成，并且共聚物中碳水化合物残基的增加导致这些聚合物的转染效率降低。研究了血清蛋白对基于统计和二嵌段共聚物的复合物的影响，并因此研究了基因传递功效。结果表明，与统计共聚物相比，Hep G2和Hela细胞中基于二嵌段共聚物的多链体与血清蛋白的相互作用较低，细胞摄取较低，基因表达非常低。

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    《Biomaterials》 |2011年第22期|共12页
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    Ahmed M; Narain R;

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