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

被引:727
作者
Tang, MX
Szoka, FC
机构
[1] UNIV CALIF SAN FRANCISCO,DEPT BIOPHARMACEUT SCI,SAN FRANCISCO,CA 94143
[2] UNIV CALIF BERKELEY,UNIV CALIF SAN FRANCISCO,JOINT GRP BIOENGN,SAN FRANCISCO,CA
关键词
compaction; DNA; gene delivery; polyamidoamine dendrimer; polyethylenimine; toroid;
D O I
10.1038/sj.gt.3300454
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:823 / 832
页数:10
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