Phosphonium-containing diblock copolymers for enhanced colloidal stability and efficient nucleic acid delivery

Sean T. Hemp, Adam E. Smith, Joshua M. Bryson, Michael H. Allen, Timothy Edward Long*

*この研究の対応する著者

研究成果: Article査読

61 被引用数 (Scopus)

抄録

RAFT polymerization successfully controlled the synthesis of phosphonium-based AB diblock copolymers for nonviral gene delivery. A stabilizing block of either oligo(ethylene glycol9) methyl ether methacrylate or 2-(methacryloxy)ethyl phosphorylcholine provided colloidal stability, and the phosphonium-containing cationic block of 4- vinylbenzyltributylphosphonium chloride induced electrostatic nucleic acid complexation. RAFT polymerization generated well-defined stabilizing blocks (Mn = 25000 g/mol) and subsequent chain extension synthesized diblock copolymers with DPs of 25, 50, and 75 for the phosphonium-containing block. All diblock copolymers bound DNA efficiently at ± ratios of 1.0 in H 2O, and polyplexes generated at ± ratios of 2.0 displayed hydrodynamic diameters between 100 and 200 nm. The resulting polyplexes exhibited excellent colloidal stability under physiological salt or serum conditions, and they maintained constant hydrodynamic diameters over 24 h. Cellular uptake studies using Cy5-labeled DNA confirmed reduced cellular uptake in COS-7 and HeLa cells and, consequently, resulted in low transfection in these cell lines. Serum transfection in HepaRG cells, which are a predictive cell line for in vivo transfection studies, showed successful transfection using all diblock copolymers with luciferase expression on the same order of magnitude as Jet-PEI. All diblock copolymers exhibited low cytotoxicity (>80% cell viability). Promising in vitro transfection and cytotoxicity results suggest future studies involving the in vivo applicability of these phosphonium-based diblock copolymer delivery vehicles.

本文言語English
ページ(範囲)2439-2445
ページ数7
ジャーナルBiomacromolecules
13
8
DOI
出版ステータスPublished - 2012 8 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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