Bioreducible Poly(amido amine) Copolymers Derived from Histamine and Agmatine for Highly Efficient Gene Delivery
Bioreducible Poly(amido amine) Copolymers Derived from Histamine and Agmatine for Highly Efficient Gene Delivery
复制标题
源自组胺和胍丁胺的生物可还原聚（酰胺基胺）共聚物，用于高效基因传递
DOI：
10.1002/pi.5728
复制
发表时间：
2018
影响因子：
3.2
通讯作者：
Pingtian Ding
中科院分区：
文献类型：
--
作者：
Yanping Sun;Hui Liu;Haonan Xing;Lang Lang;Lin Cheng;Tianzhi Yang;Li Yang;Pingtian Ding
组胺（HIS）由于其咪唑基团，可通过“质子海绵效应”促进复合物的内体逃逸。胍丁胺（Agmatine，AGM）由于其胍基的存在，可以促进复合物的跨膜过程。因此，以HIS和AGM为氨基单体，通过Michael加成与胱胺双丙烯酰胺（CBA）反应。合成的拟肽poly（CBA‐HIS/AGM）s具有高转染效率和低细胞毒性，表明其作为基因载体的巨大潜力。结果还表明，HIS和AGM对poly（CBA-HIS/AGM）的影响是不同的：HIS能提高poly（CBA-HIS/AGM）的缓冲能力和生物还原能力，而AGM能促进poly（CBA-HIS/AGM）的质粒DNA包装和浓缩能力。此外，转染机制研究结果表明，poly（CBA‐HIS/AGM）聚合物主要通过网格蛋白依赖性内吞进入细胞，并且它们可以有效地逃逸内体，表明内体逃逸不是基于这些聚合物的基因递送的限制性步骤。© 2018化学工业协会
Histamine (HIS) can facilitate the endosomal escape of polyplexes via the ‘proton sponge effect’ because of its imidazole groups. Agmatine (AGM) can improve the transmembrane process of polyplexes as a result of its guanidinium groups. Therefore, HIS and AGM were used as amino monomers to react with cystamine bisacrylamide (CBA) through Michael addition. The synthesized peptide‐mimicking poly(CBA‐HIS/AGM)s showed high transfection efficiency and low cytotoxicity, indicating their great potential as gene carriers. The results also demonstrated that the effects of HIS and AGM on the properties of poly(CBA‐HIS/AGM)s were different: HIS could increase their buffering capacities and bioreducibility, but AGM could facilitate their plasmid DNA packaging and condensing abilities. In addition, the results of transfection mechanism studies indicated that poly(CBA‐HIS/AGM) polyplexes entered into cells mainly via clathrin‐dependent endocytosis and they could efficiently escape the endosome, indicating endosomal escape was not the limiting step for gene delivery based on these polymers. © 2018 Society of Chemical Industry