Pentalysine-grafted ROMP polymers for DNA complexation and delivery

Pentalysine-grafted ROMP polymers for DNA complexation and delivery
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DOI:
10.1021/bm800511p
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发表时间:
2008-09-01
期刊:
影响因子:
6.2
通讯作者:
Emrick, Todd
Emrick, Todd
中科院分区:
化学2区
文献类型:
--
作者:
Breitenkamp, Rebecca B.;Emrick, Todd

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两亲性接枝聚合物,含有寡聚赖氨酸基团悬垂到疏水性聚环辛烯主链,用于形成与质粒DNA pZsGreen 1-N1的聚合复合物。发现这些聚(环辛烯-接枝-五赖氨酸)结构是COS-1和HeLa细胞的有效转染试剂。在聚合物le(平均聚合度为206)的情况下,发现转染后48小时的蛋白质表达水平与商业转染试剂jetPE 1和SuperFect相当或更好。对于HeLa细胞,GFP表达水平优于Lipofectamine 2000。特别令人感兴趣的是在用由戊烯基赖氨酸接枝的聚合物形成的复合物的实验中观察到的优异的细胞活力。在最高分子量接枝共聚物聚合物1 e的实施例中,相对于未处理的细胞,COS-1细胞的细胞存活率为99%,HeLa细胞的细胞存活率为92%,而商业试剂的COS-1细胞的细胞存活率为67-80%,HeLa细胞的细胞存活率为17-52%。这些聚烯烃-接枝-五赖氨酸结构作为DNA递送载体的有效性归因于它们的两亲性和支化结构。
Amphiphilic graft polymers, containing oligolysine groups pendent to a hydrophobic polycyclooctene backbone, were used to form polyplexes with plasmid DNA pZsGreen1-N1. These poly(cyclooctene-graft-pentalysine) structures were found to be effective transfection reagents for COS-1 and HeLa cells. In the case of polymer le (average degree of polymerization of 206), protein expression levels 48 h post-transfection were found to be comparable to, or better than, commercial transfection reagents jetPE1 and SuperFect. With HeLa cells, GFP expression levels were better than Lipofectamine 2000. Of particular interest was the excellent cell viability seen in experiments with polyplexes formed from the pentalysine-grafted polymers. In the example of the highest molecular weight graft copolymer, polymer 1e, cell viability relative to untreated cells was 99% with COS-1 cells and 92% with HeLa cells in contrast to the commercial reagents, which gave 67-80% with COS-1 cells and 17-52% with HeLa cells. The effectiveness of these polyolefin-graft-pentalysine structures as DNA delivery vehicles is attributed to their amphiphilic nature and branched architecture.