Linear poly(amido amine)s with secondary and tertiary amino groups and variable amounts of disulfide linkages:: Synthesis and in vitro gene transfer properties
Linear poly(amido amine)s with secondary and tertiary amino groups and variable amounts of disulfide linkages:: Synthesis and in vitro gene transfer properties
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DOI：
10.1016/j.jconrel.2006.09.009
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发表时间：
2006-11-28
影响因子：
10.8
通讯作者：
Engbersen, Johan F. J.
中科院分区：
文献类型：
--
作者：
Lin, Chao;Zhong, Zhiyuan;Engbersen, Johan F. J.
合成了一组主链含有仲胺和叔胺基团、双丙烯酰胺链段具有不同结构的新型聚（酰胺胺）均聚物和共聚物（PAA），并对其作为非病毒基因递送载体进行了评价。其中，还采用含二硫化物的胱胺双丙烯酰胺作为（共聚）单体，产生在主链中具有可变量的生物可还原二硫键的PAA。将三官能的1-（2-氨乙基）哌嗪与等摩尔量的适当的双（丙烯酰胺）进行Michael加成，得到线性聚合物，如通过它们的C-13 NMR谱所阐明的。该聚合物在pH 5.1和pH 7.4之间具有高于支化聚乙烯亚胺（pEI）的缓冲能力，并且能够有效地将DNA缩合成纳米尺寸（< 150 nm）和带正电荷的复合物。用COS-7细胞的转染实验表明，来自具有二硫键的PAA的多聚复合物比来自缺乏二硫键的PAA的多聚复合物产生显著更高的转染，并且XTT测定表明这些聚合物基本上是无毒的。二硫化物含量的变化表明，具有适当二硫化物含量的PAA共聚物的复合物具有很大程度上改善的生物物理性质，产生增强的基因表达水平沿着低毒性。结果表明，生物可还原的聚（酰胺胺）是一类非常有前途的安全和有效的基因传递聚合物。(c)2006 Elsevier B. V.保留所有权利。
A group of novel poly(amido amine) homo- and copolymers (PAAs) containing secondary and tertiary amine groups in their main chain and different structures in the bisacrylamide segments were synthesized and evaluated as non-viral gene delivery vectors. Among these, also the disulfide-containing cystaminebisacrylamide was employed as a (co)monomer, yielding PAAs with variable amounts of bioreducible disulfide linkages in the main chain. Michael addition the trifunctional 1-(2-aminoethyl) piperazine to equimolar amounts of the appropriate bis(acrylamide) yielded linear polymers as was elucidated by their C-13 NMR spectra. The polymers possess buffering capacities between pH 5.1 and pH 7.4 higher than branched polyethylenimine (pEI) and are able to efficiently condense DNA into nanosized (< 150 nm) and positively charged complexes. Transfection experiments with COS-7 cells showed that polyplexes from PAAs with disulfide linkages give significant higher transfections than those from PAAs lacking the disulfide linkage, and XTT assays showed that these polymers are essentially non-toxic. Variation of the disulfide content revealed that polyplexes of PAA copolymers with appropriate disulfide content have largely improved biophysical properties, yielding enhanced levels of gene expression along with low toxicity. The results demonstrate that bioreducible poly(amido amine)s are a very promising class of polymers for safe and efficient gene delivery. (c) 2006 Elsevier B.V. All rights reserved.