Structure-Based Design of Dendritic Peptide Bolaamphiphiles for siRNA Delivery

作者：Hanxiang Zeng, Mark E. Johnson, Nathan J. Oldenhuis, Timothy N. Tiambeng, Zhibin Guan · 发表于：ACS Central Science · 年份：2015 · DOI：10.1021/acscentsci.5b00233 · 被引用次数：64 · 研究领域：RNA Interference and Gene Delivery、Advanced biosensing and bioanalysis techniques、Dendrimers and Hyperbranched Polymers

Development of safe and effective delivery vectors is a critical challenge for the application of RNA interference (RNAi)-based biotechnologies. In this study we show the rational design of a series of novel dendritic peptide bolaamphiphile vectors that demonstrate high efficiency for the delivery of small interfering RNA (siRNA) while exhibiting low cytotoxicity and hemolytic activity. Systematic investigation into structure-property relationships revealed an important correlation between molecular design, self-assembled nanostructure, and biological activity. The unique bolaamphiphile architecture proved a key factor for improved complex stability and transfection efficiency. The optimal vector contains a fluorocarbon core and exhibited enhanced delivery efficiency to a variety of cell lines and improved serum resistance when compared to hydrocarbon analogues and lipofectamine RNAiMAX. In addition to introducing a promising new vector system for siRNA delivery, the structure-property relationships and "fluorocarbon effect" revealed herein offer critical insight for further development of novel materials for nucleic acid delivery and other biomaterial applications.