Premium
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
Accelerating Research
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom
Address
John Eccles HouseRobert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom