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阿斯特拉莫尔聚(丙烯亚胺)树枝状大分子在水和水盐溶液中与DNA及聚(甲基丙烯酸酯)阴离子的相互作用

Interaction of Astramol poly(propyleneimine) dendrimers with DNA and poly(methacrylate) anion in water and water-salt solutions.

作者信息

Zhiryakova Marina V, Izumrudov Vladimir A

机构信息

Chemistry Department, M.V. Lomonosov Moscow State University , Moscow 119991, Russia.

出版信息

J Phys Chem B. 2014 Jul 24;118(29):8819-26. doi: 10.1021/jp502953y. Epub 2014 Jul 7.

Abstract

Interaction of poly(propyleneimine) dendrimers DAB-dendr-(NH2)x of five generations (x = 4, 8, 16, 32, and 64) with either calf thymus DNA or tagged by pyrenyl groups poly(methacrylate) anion (PMA*) as well as destruction of formed polyelectrolyte complexes by the added sodium chloride were studied by fluorescence quenching techniques. DNA-containing complexes (dendriplexes) were investigated by ethidium bromide assay, whereas formation of PMA* complexes was estimated by fluorescence of the pyrenyl groups that remained free of contact with the dendrimers-quenchers. The ion pairing with DNA phosphate groups was pH-sensitive and accompanied by inaccessibility of a part of the dendrimer amino groups even in slightly acidic media. The growth of the generation number resulted in successive stabilization of the dendriplexes against the added salt. The dendriplexes of all dendrimers except DAB-dendr-(NH2)4 were stable at physiological ionic strength. In contrast to the highly charged cationic polymer poly(N-ethyl-4-vinylpyridinium) bromide of different degrees of polymerization, the dendrimers formed more stable complexes with flexible PMA* rather than with DNA, proving the inaccessibility of a part of the amino groups for the rigid double helix. The revealed regularities appear to be a platform for design of dendriplexes with controllable stability, in particular fulfilling the requirements imposed for gene delivery vehicles.

摘要

研究了五代(x = 4、8、16、32和64)的聚(丙烯亚胺)树枝状大分子DAB-dendr-(NH2)x与小牛胸腺DNA或芘基标记的聚(甲基丙烯酸酯)阴离子(PMA*)的相互作用,以及添加氯化钠对形成的聚电解质复合物的破坏作用,采用荧光猝灭技术进行研究。含DNA的复合物(树枝状复合物)通过溴化乙锭测定法进行研究,而PMA复合物的形成则通过未与树枝状大分子猝灭剂接触的芘基荧光进行估算。与DNA磷酸基团的离子配对对pH敏感,即使在微酸性介质中,部分树枝状大分子氨基也无法接近。代数的增加导致树枝状复合物对添加盐的稳定性逐渐增强。除DAB-dendr-(NH2)4外,所有树枝状大分子的树枝状复合物在生理离子强度下都是稳定的。与不同聚合度的高电荷阳离子聚合物聚(N-乙基-4-乙烯基吡啶)溴化物不同,树枝状大分子与柔性PMA形成的复合物比与DNA形成的复合物更稳定,这证明了部分氨基对于刚性双螺旋是无法接近的。所揭示的规律似乎是设计具有可控稳定性的树枝状复合物的平台,特别是满足基因传递载体的要求。

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