The influence of polymer structure on the interactions of cationic polymers with DNA and morphology of the resulting complexes

The influence of polymer structure on the interactions of cationic polymers with DNA and morphology of the resulting complexes
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DOI:
10.1038/sj.gt.3300454
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发表时间:
1997-08-01
期刊:
影响因子:
5.1
通讯作者:
Szoka, FC
Szoka, FC
中科院分区:
医学3区
文献类型:
--
作者:
Tang, MX;Szoka, FC

文献摘要

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四种用于将DNA传递到培养细胞中的阳离子聚合物:聚赖氨酸、完整的聚酰胺树状大分子、断裂的聚酰胺树状大分子和聚乙烯亚胺,研究了它们与DNA相互作用的能力。用电子显微镜检查了聚合物与DNA之间的配合物。所有带DNA的阳离子聚合物都形成了直径为55 +/- 12 nm的类似环状结构。DNA复合物被观察为单个的、不同的单位;用动态光散射法测定了它们在溶液中的视直径,范围为90 ~ 130 nm。在电子显微镜下,聚赖氨酸和完整树突状分子的DNA复合物一般呈簇状;它们在溶液中的直径均大于1000 nm,表明它们的环状配合物在溶液中聚集。阳离子聚合物与DNA结合的化学计量是伯胺与DNA磷酸盐的比例接近1:1。所有阳离子聚合物与DNA的表观结合随着离子强度的增加而线性降低,达到0.8 M NaCl。因此,在所研究的浓度下,这些聚合物与DNA发生静电相互作用,形成具有环形形态的单元结构;单元结构在溶液中的聚集程度取决于单个聚合物的特性。
Four cationic polymers used to deliver DNA into cultured cells: polylysine, intact polyamidine dendrimer, fractured polyamidoamine dendrimer and polyethylenimine, are examined for their ability to interact with DNA. Complexes between the polymers and DNA were examined using electron microscopy. Similar toroidal structures with diameters of 55 +/- 12 nm were formed from all of the cationic polymers with DNA. The DNA complexes were observed as single, distinct units; their apparent diameters in solution aas measured by dynamic light scattering ranged from 90 to 130 nm. The DNA complexes of polylysine and intact dendrimer generally appeared as clusters in electron micrographs; their diameters in solution were larger than 1000 nm, which suggests that their toroidal complexes aggregate in solution. The cationic polymers bind to DNA in a stoichiometry that is nearly 1:1 in primary amines to DNA phosphates. The apparent binding of all cationic polymers to DNA decreases linearly with increasing ionic strength, up to 0.8 M NaCl. Thus, at the concentrations studied these polymers interact electrostatically with DNA forming a unit structure with toroidal morphology; the extent of aggregation of the unit structures in solution depends upon the characteristics of the individual polymer.