Random and block copolymers of bioreducible poly(amido amine)s with high- and low-basicity amino groups: Study of DNA condensation and buffer capacity on gene transfection
Random and block copolymers of bioreducible poly(amido amine)s with high- and low-basicity amino groups: Study of DNA condensation and buffer capacity on gene transfection
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DOI：
10.1016/j.jconrel.2007.07.006
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发表时间：
2007-10-18
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.
以N，N '-胱胺双丙烯酰胺（CBA）和两种胺类单体，组胺（HIS）和3-（二甲氨基）-1-丙胺（DMPA）。含有可变HIS/DMPA比率的共聚物显示出比p（CBA-HIS）均聚物更高的结合DNA的能力，并且将DNA缩合成具有比p（CBA-HIS）的聚合复合物（类似于220 nm）更小的粒径（< 150 nm）的聚合复合物。共聚物的缓冲容量随着HIS/DMPA比例的增加而增加。这些共聚物能够体外转染COS-7细胞，其效率随着HIS/DMPA比率的增加而增加。HIS/DMPA比率为70/30的无规和嵌段共聚物结合了最佳的DNA缩合能力和缓冲能力，从而与p（CBA-HIS）均聚物相比，在不存在和存在血清的情况下诱导更高的转染效率。此外，无规和嵌段共聚物显示出相似的转染能力，但两者都具有比p（CBA-MS）和p（CBA-DMPA）均聚物的物理混合物更高的能力。XTT试验表明，当观察到最高的转染活性时，SS-PAA共聚物的聚合复合物具有基本上低的细胞毒性。(c)2007 Elsevier B. V.保留所有权利。
Poly(amido amine) (SS-PAA) random and block copolymers having bioreducible disulfide bonds in the main chain and amino groups with distinctly different basicity in the side chain were designed and synthesized by Michael addition polymerization between N, N'-cystaminebisacrylamide (CBA) and two amine monomers, i.e., histamine (HIS) and 3-(dimethylamino)-1-propylamine (DMPA). Copolymers containing variable HIS/DMPA ratios show higher ability to bind DNA than p(CBA-HIS) homopolymer and condense DNA into the polyplexes with particle sizes (< 150 nm) that are smaller than polyplexes of p(CBA-HIS) (similar to 220 nm). The buffer capacities of the copolymers increase with increasing HIS/DMPA ratio. These copolymers are able to transfect COS-7 cells in vitro with efficiencies that increase with increasing HIS/DMPA ratio. The random and block copolymers at a HIS/DMPA ratio of 70/30 combines optimal DNA condensation capability and buffer capacity, thereby inducing higher transfection efficiency in the absence and presence of serum as compared to p(CBA-HIS) homopolymer. Moreover, random and block copolymers show a similar transfection capacity, but both have higher capacity than the physical mixtures of p(CBA-MS) and p(CBA-DMPA) homopolymers. XTT assay reveals that the polyplexes of the SS-PAA copolymers have essentially low cytotoxicity when the highest transfection activity is observed. (c) 2007 Elsevier B.V. All rights reserved.