Tailoring charge density and hydrogen bonding of imidazolium copolymers for efficient gene delivery

Michael H. Allen, Matthew D. Green, Hiwote K. Getaneh, Kevin M. Miller, Timothy Edward Long

研究成果: Article査読

64 被引用数 (Scopus)

抄録

Conventional free radical polymerization with subsequent postpolymerization modification afforded imidazolium copolymers with controlled charge density and side chain hydroxyl number. Novel imidazolium-containing copolymers where each permanent cation contained one or two adjacent hydroxyls allowed precise structure-transfection efficiency studies. The degree of polymerization was identical for all copolymers to eliminate the influence of molecular weight on transfection efficiency. DNA binding, cytotoxicity, and in vitro gene transfection in African green monkey COS-7 cells revealed structure-property- transfection relationships for the copolymers. DNA gel shift assays indicated that higher charge densities and hydroxyl concentrations increased DNA binding. As the charge density of the copolymers increased, toxicity of the copolymers also increased; however, as hydroxyl concentration increased, cytotoxicity remained constant. Changing both charge density and hydroxyl levels in a systematic fashion revealed a dramatic influence on transfection efficiency. Dynamic light scattering of the polyplexes, which were composed of copolymer concentrations required for the highest luciferase expression, showed an intermediate DNA-copolymer binding affinity. Our studies supported the conclusion that cationic copolymer binding affinity significantly impacts overall transfection efficiency of DNA delivery vehicles, and the incorporation of hydroxyl sites offers a less toxic and effective alternative to more conventional highly charged copolymers.

本文言語English
ページ(範囲)2243-2250
ページ数8
ジャーナルBiomacromolecules
12
6
DOI
出版ステータスPublished - 2011 6月 13
外部発表はい

ASJC Scopus subject areas

  • バイオエンジニアリング
  • 材料化学
  • ポリマーおよびプラスチック
  • 生体材料

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