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阳离子含氟两亲性接枝共聚物作为 DNA 载体。

Cationic fluorine-containing amphiphilic graft copolymers as DNA carriers.

机构信息

Ministry-of-Education Key Laboratory for the Green Preparation and Application of Functional Materials, Hubei University, Wuhan 430062, China.

出版信息

Biomaterials. 2010 Mar;31(9):2673-85. doi: 10.1016/j.biomaterials.2009.12.014. Epub 2010 Jan 19.

DOI:10.1016/j.biomaterials.2009.12.014
PMID:20034666
Abstract

A series of cationic fluorine-containing amphiphilic graft copolymers P(HFMA-St-MOTAC)-g-PEG comprising poly(hexafluorobutyl methacrylate) (PHFMA) poly(methacryl oxyethyl trimethylammonium chloride) (PMOTAC) polystyrene (PSt) backbones and poly(ethylene glycol) (PEG) side chains are synthesized as a type of non-viral gene vector. The copolymers self-assemble into spherical micelles in the aqueous media and turbidity and cytotoxicity measurements show that those micelles have excellent dispersive stability and low cytotoxicity. The interactions between the copolymers and calf-thymus DNA are studied by fluorescence spectroscopy and viscosity. The former discloses electrostatic interaction, hydrophobic interaction, and hydrogen bonding in the copolymer/DNA system, whereas the latter indicates that these graft copolymers can bind DNA via the electrostatic and classical intercalation modes. The DNA-binding capacity determined by the gel retardation assay and UV-visible spectrophotometry shows that the copolymers have good binding capacity to DNA and a high charge density or HFMA content in the copolymers bode well for DNA-binding. Transmission electron microscopy, photon correlation spectroscopy, and zeta potential data reveal that stable colloidal complexes (particles) can form easily between the copolymer micelles and DNA. Our results suggest that the copolymers are a promising non-viral vector in a gene delivery system.

摘要

一系列包含聚(六氟丁基甲基丙烯酸酯)(PHFMA)、聚(甲基丙烯氧基乙基三甲基氯化铵)(PMOTAC)聚苯乙烯(PSt)主链和聚乙二醇(PEG)侧链的阳离子含氟两亲性接枝共聚物 P(HFMA-St-MOTAC)-g-PEG 被合成作为一种非病毒基因载体。共聚物在水介质中自组装成球形胶束,浊度和细胞毒性测量表明这些胶束具有优异的分散稳定性和低细胞毒性。荧光光谱和粘度研究了共聚物与小牛胸腺 DNA 之间的相互作用。前者揭示了共聚物/DNA 体系中的静电相互作用、疏水相互作用和氢键,而后者表明这些接枝共聚物可以通过静电和经典嵌入模式结合 DNA。凝胶阻滞实验和紫外可见分光光度法测定的 DNA 结合能力表明,共聚物对 DNA 具有良好的结合能力,共聚物中的高电荷密度或 HFMA 含量有利于 DNA 结合。透射电子显微镜、光子相关光谱和zeta 电位数据表明,共聚物胶束与 DNA 之间很容易形成稳定的胶体复合物(颗粒)。我们的结果表明,这些共聚物是基因传递系统中一种有前途的非病毒载体。

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