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Polycationic adamantane-based dendrons form nanorods in complex with plasmid DNA

机译：基于聚酰胺基烷烷基的树枝状纳米棒与质粒DNA复合物

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摘要

Nonviral vectors such as cationic dendrimers and dendrons are demonstrating great properties for their use as gene delivery systems. A good carrier has to efficiently bind and protect the genetic material, but many of the newly developed vectors already fail at this initial step. A continuous and rational design of novel molecular structures is therefore beneficial to this field. Here we report the study of the complexation between different polycationic adamantane-based dendrons, called HYDRAmers, with a model plasmid DNA (pDNA). The role of the dendron generation, the cationic periphery and the functionalization at the focal point on the binding has been thoroughly evaluated. We discovered how appropriate chemical modifications could improve efficiently the complexation to get HYDRAplexes with very good pDNA binding and protecting properties. Despite these favorable characteristics, the unexpected morphology of the complexes forming long nanorods can explain the relatively low transfection performance. Both the reported literature data that guided us for the design of the HYDRAmers and the lessons learned from this work should broadly inform for future development of well-defined gene carriers. Our results also strongly encourage to proceed on the study of the polycationic adamantane-based dendrons for alternative therapies like gene silencing.
机译：阳离子树枝状大分子和树枝等非血管载体正在展示其作为基因递送系统的优异性质。良好的载体必须有效地结合和保护遗传物质，但许多新发达的矢量在这个初始步骤中已经失败了。因此，新的分子结构的连续和合理的设计对该领域有益。在这里，我们报告了研究不同聚阳离子亚烷烷基的树枝状的络合，称为多豪液，具有模型质粒DNA（PDNA）。已经彻底评估了Dendron生成，阳离子周边和官能化在结合上的焦点的作用。我们发现有效的化学修饰如何有效地改善络合，以使Hydraphys具有非常好的PDNA结合和保护性能。尽管具有这些有利的特性，但形成长纳米棒的复合物的意外形态可以解释相对低的转染性能。引用我们为多名流门设计的文献数据以及从这项工作中汲取的经验教训应该广泛地通知未来明确定义的基因载体的发展。我们的结果还强烈鼓励继续研究基于聚酰胺基丹烷的树突，以获得基因沉默等替代疗法。

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  • 来源
    《RSC Advances》 |2016年第49期|共10页
  • 作者

    Grillaud Maxime; de Garibay Aritz Perez Ruiz; Bianco Alberto;

  • 作者单位

    CNRS Inst Biol Mol &

    Cellulaire Immunopathol &

    Chim Th F-67000 Strasbourg France;

    CNRS Inst Biol Mol &

    Cellulaire Immunopathol &

    Chim Th F-67000 Strasbourg France;

    CNRS Inst Biol Mol &

    Cellulaire Immunopathol &

    Chim Th F-67000 Strasbourg France;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 化学;
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