title: Structure-Based Design of Dendritic Peptide Bolaamphiphiles for siRNA Delivery.
abstract: 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.
authors.affiliation: Department of Chemistry, University of California , Irvine, California 92697, United States.
authors.forename: Hanxiang
authors.initials: H
authors.lastname: Zeng
authors.affiliation: Department of Chemistry, University of California , Irvine, California 92697, United States.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Johnson
authors.affiliation: Department of Chemistry, University of California , Irvine, California 92697, United States.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Oldenhuis
authors.affiliation: Department of Chemistry, University of California , Irvine, California 92697, United States.
authors.forename: Timothy N
authors.initials: TN
authors.lastname: Tiambeng
authors.affiliation: Department of Chemistry, University of California , Irvine, California 92697, United States.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Guan