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首页> 外文期刊>Acta biomaterialia >Cyclen-based lipidic oligomers as potential gene delivery vehicles
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Cyclen-based lipidic oligomers as potential gene delivery vehicles

机译：基于Cyclenn的脂质寡聚体作为潜在的基因传递载体

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A series of cyclen-based linear oligomers bearing hydrophobic long chains (lipopolymers Cy-LC, where Cy and LC represent cyclen-based linear backbone and hydrophobic long chain substituents, respectively) were designed and synthesized. The effects of type and degree of substitution (DS) of hydrophobic long chains on the transfection efficiency were systematically studied. The nitrogen atoms with relatively strong basicity on the cyclen ensure their good DNA binding ability, which was confirmed by gel retardation and ethidium bromide exclusion assays. Lipopolyplexes could be formed as nanoparticles with suitable sizes and zeta potentials for gene transfection. In vitro gene delivery experiments revealed that the linoleic acid (LIN) substituted material Cy-LIN has better transfection efficiency than 25 kDa polyethylenimine in the absence or in the presence of serum. 3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide and hemolysis assays showed low cytotoxicity and good biocompatibility of the lipopolyplexes. Fluorescent labeled DNA was used to study the cellular uptake and intracellular distribution of transfected DNA. Flow cytometry results suggested that a long chain is necessary for efficient cellular uptake, and images from confocal laser scanning microscopy showed that after 4 h transfection, most of the fluorescent labeled DNA accumulated in the perinuclear region, which was required for efficient gene expression. Moreover, it was also found that the DS of the hydrophobic moiety can adjust the balance between DNA binding ability and dissociation of polyplexes, significantly affecting the transfection efficiency.
机译：设计并合成了一系列带有疏水性长链的基于周期蛋白的线性低聚物（脂聚合物Cy-LC，其中Cy和LC分别表示基于周期蛋白的线性主链和疏水性长链取代基）。系统研究了疏水长链的类型和取代度（DS）对转染效率的影响。在细胞周期蛋白上具有较强碱性的氮原子可确保其良好的DNA结合能力，这已通过凝胶阻滞和溴化乙锭排阻分析得到了证实。脂质多聚体可以形成为具有合适大小和ζ电势用于基因转染的纳米颗粒。体外基因传递实验表明，在不存在或存在血清的情况下，亚油酸（LIN）取代的材料Cy-LIN的转染效率高于25 kDa聚乙烯亚胺。 3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴化物和溶血试验显示脂多糖的低细胞毒性和良好的生物相容性。荧光标记的DNA用于研究转染DNA的细胞摄取和细胞内分布。流式细胞仪结果表明，长链是有效摄取细胞所必需的，而共聚焦激光扫描显微镜的图像显示，转染4 h后，大多数荧光标记的DNA积累在核周区域，这是有效基因表达所必需的。此外，还发现疏水部分的DS可以调节DNA结合能力和多聚体解离之间的平衡，从而显着影响转染效率。

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