Multiplexed supramolecular self-assembly for non-viral gene delivery

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• 作者：Nathan P. Gabrielson ; Jianjun Cheng
• 关键词：Non-viral gene delivery ; Self-assembly ; Spermine ; Oleic acid ; Oligoarginine ; Folic acid
• 刊名：Biomaterials
• 出版年：2010
• 出版时间：December 2010
• 年：2010
• 卷：31
• 期：34
• 页码：9117-9127
• 全文大小：1571 K

文摘

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.