title: Poly(Amido Amine)s Containing Agmatine and Butanol Side Chains as Efficient Gene Carriers.
abstract: A new type of bioreducible poly(amido amine) copolymer is synthesized by the Michael addition polymerization of cystamine bisacrylamide (CBA) with 4-aminobutylguanidine (agmatine, AGM) and 4-aminobutanol (ABOL). Since the positively charged guanidinium groups of AGM and the hydroxybutyl groups of ABOL in the side chains have shown to improve the overall transfection efficiency of poly(amido amine)s, it is hypothesized that poly(CBA-ABOL/AGM) synthesized at the optimal ratio of both components would result in high transfection efficiency and minimal toxicity. In this study, a series of the poly(CBA-ABOL/AGM) copolymers is synthesized as gene carriers. The polymers are characterized and luciferase transfection efficiencies of the polymers in various cell lines are investigated to select the ideal ratio between AGM and ABOL. The poly(CBA-ABOL/AGM) containing 80% AGM and 20% ABOL has shown the best transfection efficiency with the lowest cytotoxicity, indicating that this polymer is very promising as a potent and nontoxic gene carrier.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah, USA.|Division of Cardiothoracic Surgery, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah, USA.
authors.forename: Young-Wook
authors.initials: YW
authors.lastname: Won
authors.affiliation: Department of Biomedical Chemistry, MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, University of Twente, Enschede, The Netherlands.
authors.forename: Marc
authors.initials: M
authors.lastname: Ankoné
authors.affiliation: Department of Biomedical Chemistry, MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, University of Twente, Enschede, The Netherlands.
authors.forename: Johan F J
authors.initials: JF
authors.lastname: Engbersen
authors.affiliation: Department of Biomedical Chemistry, MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, University of Twente, Enschede, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Feijen
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Sung Wan
authors.initials: SW
authors.lastname: Kim
mesh_terms: D000376:Agmatine / Q000737:chemistry* / Q000494:pharmacology; D000605:Amino Alcohols / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003538:Cystamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D015870:Gene Expression; D017930:Genes, Reporter; D057809:HEK293 Cells; D006801:Humans; D007773:Lactates / Q000737:chemistry* / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D010084:Oxidation-Reduction; D058105:Polymerization; D014162:Transfection / Q000379:methods*
chemical_list: D000605:Amino Alcohols; D007773:Lactates; C113063:cystamine bislactamide; C089584:4-aminobutanol; D000376:Agmatine; D008156:Luciferases; D003538:Cystamine
keywords: biological applications of polymers; drug delivery systems; gene delivery; nanoparticles; structure-property relations; transfection