Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Biomaterials. 2010 Dec;31(34):9117-27. doi: 10.1016/j.biomaterials.2010.08.024. Epub 2010 Sep 1.
Recently, there has been success in applying a semi-rational approach to non-viral gene delivery vector development using a combinatorial/parallel synthesis approach to construct libraries of materials with unique molecular structures. In this approach, it is hoped that the random incorporation of various hydrophobic and hydrophilic domains in the library will yield candidates with the appropriate balance of DNA binding strength and endosomolytic properties to yield efficient gene delivery. Herein we describe a library approach to gene delivery vector development that relies on the supramolecular self-assembly of individual components instead of chemical reaction. Each component in the described system is capable of performing a single and well-defined purpose--DNA binding (dioleylspermine), membrane permeation (oligoarginine) or targeting (folic acid). A combination of electrostatic attraction and the hydrophobic effect is used to bring the individual groups together to form nanoscale complexes with DNA. Because the components responsible for DNA binding, membrane permeation and targeting are separate, it is possible to alter the balance between hydrophilic and hydrophobic groups by varying the relative amounts in the final formulation. By doing so, we can readily identify cell-specific formulations that have greater transfection efficiency than the individual components and have superior transfection efficiency to lipofectamine 2000 under similar conditions.
最近，人们成功地应用半理性方法开发非病毒基因传递载体，采用组合/平行合成方法构建具有独特分子结构的材料库。在这种方法中，希望库中各种疏水区和亲水区的随机掺入将产生具有适当 DNA 结合强度和内体溶解特性平衡的候选物，从而产生有效的基因传递。本文描述了一种基于超分子自组装的基因传递载体开发的方法，而不是依赖于化学反应。描述系统中的每个组件都能够执行单一且明确的功能-DNA 结合（二油酰基精胺），膜渗透（寡精氨酸）或靶向（叶酸）。静电吸引和疏水作用的组合用于将各个基团聚集在一起，形成具有 DNA 的纳米级复合物。由于负责 DNA 结合，膜渗透和靶向的组分是分开的，因此通过改变最终配方中相对量，可以改变亲水区和疏水区之间的平衡。通过这样做，我们可以很容易地确定比单个成分具有更高转染效率的细胞特异性配方，并且在相似条件下比脂质体 2000 具有更高的转染效率。
