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Bioreducible poly(amido amine) copolymers derived from histamine and agmatine for highly efficient gene delivery
Author(s) -
Sun Yanping,
Liu Hui,
Xing Haonan,
Lang Lang,
Cheng Lin,
Yang Tianzhi,
Yang Li,
Ding Pingtian
Publication year - 2019
Publication title -
polymer international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.592
H-Index - 105
eISSN - 1097-0126
pISSN - 0959-8103
DOI - 10.1002/pi.5728
Subject(s) - agmatine , gene delivery , transfection , endocytosis , chemistry , endosome , michael reaction , cytotoxicity , pinocytosis , cationic polymerization , amine gas treating , monomer , polymer , polymer chemistry , biophysics , combinatorial chemistry , biochemistry , amino acid , organic chemistry , gene , cell , biology , in vitro , arginine , catalysis
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