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Melittin derived peptides for nanoparticle based siRNA transfection

Paper ID Volume ID Publish Year Pages File Format Full-Text
6275 471 2013 10 PDF Available
Title
Melittin derived peptides for nanoparticle based siRNA transfection
Abstract

Traditional transfection agents including cationic lipids and polymers have high efficiency but cause cytotoxicity. While cell penetrating peptide based transfection agents exhibit improved cytotoxicity profiles, they do not have the efficiency of existing lipidic agents due to endosomal trapping. As a consequence, we propose an alternative method to efficient peptide based siRNA transfection by starting with melittin, a known pore-forming peptide. By incorporating modifications to decrease cytotoxicity and improve siRNA binding, we have developed p5RHH, which can complex siRNA to form nanoparticles of 190 nm in diameter. p5RHH exhibits high efficiency with GFP knockdown at concentrations as low as 5 nM, with negligible cytotoxicity. To date, p5RHH has shown the ability to transfect B16 cells, Human Umbilical Vein Endothelial Cells, and RAW264.7 cells with high efficiency. These in vitro models demonstrate that p5RHH mediated transfection can block cancer cell proliferation, angiogenesis, and foam cell formation. Moreover, p5RHH/siRNA nanoparticles maintain their size and transfection efficiency in the presence of serum proteins suggesting the potential for use of p5RHH in vivo. These data suggest that our strategy for development of siRNA transfecting peptides can provide an avenue to safe and effective siRNA therapeutics.

Keywords
Drug delivery; Nanoparticle; Gene therapy; Macrophage; Endothelial cell
First Page Preview
Melittin derived peptides for nanoparticle based siRNA transfection
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 34, Issue 12, April 2013, Pages 3110–3119
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering