Dynamic Amphiphile Libraries To Screen for the 鈥淔ragrant鈥?Delivery of siRNA into HeLa Cells and Human Primary Fibroblasts

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• 作者：Charlotte Gehin ; Javier Montenegro ; Eun-Kyoung Bang ; Ana Cajaraville ; Shota Takayama ; Hisaaki Hirose ; Shiroh Futaki ; Stefan Matile ; Howard Riezman
• 刊名：The Journal of the American Chemical Society
• 出版年：2013
• 出版时间：June 26, 2013
• 年：2013
• 卷：135
• 期：25
• 页码：9295-9298
• 全文大小：405K
• 年卷期：v.135,no.25(June 26, 2013)
• ISSN：1520-5126

文摘

Dynamic amphiphiles are amphiphiles with dynamic covalent bridges between their hydrophilic heads and their hydrophobic tails. Their usefulness to activate ion transporters, for odorant release, and for differential sensing of odorants and perfumes, has been demonstrated recently. Here, we report that the same 鈥渇ragrant鈥?dynamic amphiphiles are ideal to screen for new siRNA transfection agents. The advantages of this approach include rapid access to fairly large libraries of complex structures, and possible transformation en route to assist uptake and minimize toxicity. We report single-component systems that exceed the best commercially available multicomponent cocktails with regard to both efficiency and velocity of EGFP knockdown in HeLa cells. In human primary fibroblasts, siRNA-mediated enzyme knockdown nearly doubled from >30% for Lipofectamine to >60% for our best hit. The identified structures were predictable neither from literature nor from results in fluorogenic vesicles and thus support the importance of conceptually innovative screening approaches.