title: Synthesis of Water-Soluble Imidazolium Polyesters as Potential Nonviral Gene Delivery Vehicles.
abstract: The inherent hydrolytic reactivity of polyesters renders them excellent candidates for a variety of biomedical applications. Incorporating ionic groups further expands their potential impact, encompassing charge-dependent function such as deoxyribonucleic acid (DNA) binding, antibacterial properties, and pH-responsiveness. Catalyst-free and solvent-free polycondensation of a bromomethyl imidazolium-containing (BrMeIm) diol with neopentylglycol (NPG) and adipic acid (AA) afforded novel charged copolyesters with pendant imidazolium sites. Varying ionic content influenced thermal properties and offered a wide-range, -41 to 40 °C, of composition-dependent glass transition temperatures (Tgs). In addition to desirable melt and thermal stability, polyesters with ionic concentrations ≥15 mol % readily dispersed in water, suggesting potential as nonviral gene delivery vectors. An electrophoretic gel shift assay confirmed the novel cationic copolyesters successfully bound DNA at an N/P ratio of 4 for 50 mol % and 75 mol % charged copolyesters (P(NA50-co-ImA50) and P(NA25-co-ImA75)), and an N/P ratio of 5 for 100 mol % Im (PImA). Polyplexes exhibited insignificant cytotoxicity even at high concentrations (200 μg/mL), and a Luciferase transfection assay revealed the ionic (co)polyesters transfected DNA significantly better than the untreated controls. The successful transfection of these novel (co)polyesters inspires future imidazolium-containing polyester design.
authors.affiliation: Macromolecules Innovation Institute, Department of Chemistry, Virginia Tech , Blacksburg, Virginia 24061, United States.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Nelson
authors.affiliation: School of Biomedical Engineering and Science, Virginia Tech , Blacksburg, Virginia 24061, United States.
authors.forename: Allison M
authors.initials: AM
authors.lastname: Pekkanen
authors.affiliation: Macromolecules Innovation Institute, Department of Chemistry, Virginia Tech , Blacksburg, Virginia 24061, United States.
authors.forename: Neil L
authors.initials: NL
authors.lastname: Forsythe
authors.affiliation: Macromolecules Innovation Institute, Department of Chemistry, Virginia Tech , Blacksburg, Virginia 24061, United States.
authors.forename: John H
authors.initials: JH
authors.lastname: Herlihy
authors.affiliation: Macromolecules Innovation Institute, Department of Chemistry, Virginia Tech , Blacksburg, Virginia 24061, United States.
authors.forename: Musan
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Macromolecules Innovation Institute, Department of Chemistry, Virginia Tech , Blacksburg, Virginia 24061, United States.
authors.forename: Timothy E
authors.identifier: 0000-0001-9515-5491
authors.initials: TE
authors.lastname: Long
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D007093:Imidazoles / Q000737:chemistry*; D008156:Luciferases / Q000378:metabolism; D011091:Polyesters / Q000138:chemical synthesis* / Q000494:pharmacology*; D012995:Solubility; D012997:Solvents; D014162:Transfection; D014867:Water / Q000737:chemistry*
chemical_list: D007093:Imidazoles; D011091:Polyesters; D012997:Solvents; D014867:Water; D008156:Luciferases