Poly(Amido Amine)s Containing Agmatine and Butanol Side Chains as Efficient Gene Carriers.

Poly(Amido Amine)s Containing Agmatine and Butanol Side Chains as Efficient Gene Carriers.
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DOI:
10.1002/mabi.201500369
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发表时间:
2016-04
影响因子:
4.6
通讯作者:
Kim SW
Kim SW
中科院分区:
工程技术3区
文献类型:
--
作者:
Won YW;Ankoné M;Engbersen JF;Feijen J;Kim SW

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以半胺双丙烯酰胺(CBA)、4-氨基丁基胍(AGM)和4-氨基丁醇(ABOL)为原料,通过Michael加成反应合成了一种新型的可生物还原的聚酰胺-胺共聚物。由于AgM上的正电基团和侧链上的ABOL上的羟丁基可以提高聚氨基胺S的整体转染率,因此假设在两者的最佳比例下合成的Poly(CBA-AgO/AgM)具有较高的转染率和最低的毒性。在本研究中,我们合成了一系列聚(CBA-ABOL/AGM)共聚物作为基因载体。对聚合物进行了表征,并研究了聚合物在不同细胞系中的荧光素酶转染率,以选择AGM和ABOL之间的理想比例。含有80%AGM和20%Abol的聚(CBA-ABOL/AGM)显示出最好的转染率和最低的细胞毒性,表明该聚合物作为一种有效的、无毒的基因载体是非常有前途的。
A new type of bioreducible poly(amido amine) copolymer is synthesized by the Michael addition polymerization of cystamine bisacrylamide (CBA) with 4-aminobutylguanidine (agmatine, AGM) and 4-aminobutanol (ABOL). Since the positively charged guanidinium groups of AGM and the hydroxybutyl groups of ABOL in the side chains have shown to improve the overall transfection efficiency of poly(amido amine)s, it is hypothesized that poly(CBA-ABOL/AGM) synthesized at the optimal ratio of both components would result in high transfection efficiency and minimal toxicity. In this study, a series of the poly(CBA-ABOL/AGM) copolymers is synthesized as gene carriers. The polymers are characterized and luciferase transfection efficiencies of the polymers in various cell lines are investigated to select the ideal ratio between AGM and ABOL. The poly(CBA-ABOL/AGM) containing 80% AGM and 20% ABOL has shown the best transfection efficiency with the lowest cytotoxicity, indicating that this polymer is very promising as a potent and nontoxic gene carrier.