Lipoplexes with pH-sensitive conformational switch for siRNA delivery

Document Type

Poster

Conference Title/Conference Publication

246th National Meeting and Exposition of American Chemical Society (ACS)

Organization

American Chemical Society (ACS)

Location

Indianapolis, IN

Conference Dates

September 8-12, 2013

Date of Presentation

9-8-2013

Abstract

siRNA represents a promising category of therapeutic agents for the treatment of viral and genetic diseases. However, successful gene knockdown by siRNA depends on its efficient delivery into target cells. Previously, we have reported pH-sensitive liposomes with conformational switch (Fliposomes) as a potential delivery system for small-molecule drugs and biomacromolecules. In this study, we prepared complexes of cationic Fliposomes and siRNA to transfect T47D-KBluc cells (human breast cancer), which stably express firefly luciferase. The cationic Fliposomes and their complexes with siRNA were prepared either with or without poly-L-glutamic acid (PG) as a stabilizer. Electrophoresis studies indicated that PG improved the stability of the Fliposome-siRNA complexes. Significantly more efficient knockdown of the luciferase activity was achieved by the Fliposome/siRNA complexes compared to liposome/siRNA complexes containing the common cationic lipid DOTAP.

PG also enhanced the transfection efficiency of the complexes in T47D-KBluc cells. Two other mammalian cell lines expressing GFP (green fluorescent protein) were also investigated as potential cell lines to evaluate the efficiency of siRNA delivery by Fliposomes.

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