Bioreducible poly(amido amine) copolymers derived from histamine and agmatine for highly efficient gene delivery. Issue 3 (27th November 2018)

• Record Type: Journal Article
• Authors: Sun, Yanping; Liu, Hui; Xing, Haonan; Lang, Lang; Cheng, Lin; Yang, Tianzhi; Yang, Li; Ding, Pingtian
• Is Part Of: Polymer international. Volume 68:Issue 3(2019)
• Page Start: 447
• Page End: 455
• Publication Date: 2018-11-27
• Subjects: gene delivery -- bioreducible polymers -- peptide‐mimicking -- endosomal escape -- nuclear entry; Plastics -- Periodicals; Polymers -- Periodicals; Polymerization -- Periodicals; 547.7
• DOI: 10.1002/pi.5728
• Languages: English
• ISSNs: 0959-8103

Abstract

Abstract: 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 Abstract : A new type of bioreducible poly(amido amine) copolymer is synthesized. These smart polymers could efficiently condense plasmid DNA, successfully deliver it into cells, and finally facilitate gene expression.