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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.

SUBMITTER: Zeng H 

PROVIDER: S-EPMC4582325 | biostudies-literature |

REPOSITORIES: biostudies-literature

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