Hydrolyzable p(DMAPEMA) polymers for gene delivery
Hydrolyzable p(DMAPEMA) polymers for gene delivery
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DOI：
10.1002/mabi.200600071
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发表时间：
2006-07-14
影响因子：
4.6
通讯作者：
Delair, Thierry
中科院分区：
文献类型：
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作者：
Veron, Laurent;Ganee, Arnaud;Delair, Thierry
阳离子聚合物作为转染剂的效率被认为与它们的DNA缔合/解离性质密切相关。不完全的聚合物-DNA解离可以解释用p（DMAEMA）聚合物获得的相对低的基因表达。我们的方法是合成一个p（DMAEMA）类似物，p（DMAPEMA），携带一个可水解的阳离子基团纳入侧链，以期提高转染。通过琼脂糖凝胶电泳，大小和zeta电位测量，以及由阴离子聚合物，氢氧化钠或热处理后的多聚物的解离，研究了DNA与这两种聚合物的络合。与Exgen 500相比，用293 T和BHK 21细胞评价聚合复合物的转染效率。P（DMAPEMA）聚合物能够复合DNA，并在碱处理或37 ℃储存后以游离的完整形式释放DNA。聚（天冬氨酸）是无法解离的p（DMAPEMA）为基础的复合物，与p（DMAEMA）的。未转染。用两种细胞系用p（DMAPEMA）获得。生理条件下的缓慢水解导致DNA解包或内体截留的缺乏可以解释这些结果。用能够通过静电相互作用解离的复合物而不是需要水解机制将游离DNA释放到细胞中的复合物获得更好的转染结果。
The efficiency of cationic polymers as transfectants is thought to be closely related to their DNA association/dissociation properties. An incomplete polymer-DNA dissociation could explain the relatively low gene expression obtained with p(DMAEMA) polymers. Our approach was to synthesize a p(DMAEMA) analogue, p(DMAPEMA), bearing an hydrolyzable cationic group incorporated into the pendant chain with a view to improving transfection. The complexation of DNA with both polymers was studied by agarose gel electrophoresis, size and zeta potential measurements, as well as the dissociation of the polyplexes, after treatment by an anionic polymer, sodium hydroxide or heat. The transfection efficiencies of the polyplexes were evaluated with 293T and BHK21 cells in comparison with Exgen 500. P(DMAPEMA) polymers were able to complex DNA and to release it in a free intact form after an alkaline treatment or storage at 37 degrees C. Poly(aspartic acid) was unable to dissociate p(DMAPEMA) based polyplexes, in contrast to p(DMAEMA) ones. No transfection was. obtained with p(DMAPEMA) with both cell lines. A slow hydrolysis under physiological conditions resulting in the absence of DNA unpacking or endosomal entrapment could explain these results. Better transfection results were obtained with polyplexes which were able to be dissociated by electrostatic interactions rather than ones which required the hydrolysis mechanism to release free DNA into cells.