Multiplexed supramolecular self-assembly for non-viral gene delivery.
Multiplexed supramolecular self-assembly for non-viral gene delivery.
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DOI：
10.1016/j.biomaterials.2010.08.024
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发表时间：
2010-12
期刊：
影响因子：
14
通讯作者：
Cheng, Jianjun
中科院分区：
文献类型：
--
作者：
Gabrielson, Nathan P.;Cheng, Jianjun
最近，已经成功地将半理性方法应用于非病毒基因递送载体开发，其使用组合/平行合成方法来构建具有独特分子结构的材料文库。在这种方法中，希望在文库中随机掺入各种疏水和亲水结构域将产生具有DNA结合强度和内体溶解性质的适当平衡的候选物，以产生有效的基因递送。在此，我们描述了一种基因递送载体开发的文库方法，该方法依赖于单个组分的超分子自组装而不是化学反应。所述系统中的每个组件都能够执行单一且明确定义的目的--DNA结合（二油基精胺）、膜渗透（寡聚精氨酸）或靶向（叶酸）。静电吸引和疏水效应的组合用于将各个基团聚集在一起，以形成与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，因此可以通过改变最终制剂中的相对量来改变亲水基团和疏水基团之间的平衡。通过这样做，我们可以容易地鉴定出比单独组分具有更高转染效率并且在类似条件下具有比lipofectamine 2000更上级转染效率的细胞特异性制剂。
Recently, there has been success 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.
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