Proteinase K-containing lipid nanoparticles for therapeutic delivery of siRNA LOR-1284.

Kim DC, Cho YA, Li H, Yung BC, Lee RJ
Anticancer Res 34 3531-5 07/01/2014

Abstract

BACKGROUND: The objective of the present study was to develop an efficient delivery vehicle for siRNA LOR-1284 through incorporation of proteinase K (PrK) as a means of preventing siRNA degradation by serum nucleases. Lipid nanoparticle-PrK-siRNA (LN-PrK-siRNA) complexes were synthesized and characterized.

MATERIALS AND METHODS: siRNA complexed with PrK and liposomes composed of dimethyldioctadecyl ammonium bromide/cholesterol/Tween 80 (60:35:5 molar ratio) were investigated for down-regulation of R2 mRNA activity in KB human carcinoma cells.

RESULTS: Treatment with LN-PrK-siRNA (30:0.3:1 molar ratio) significantly reduced levels of R2 mRNA compared to siRNA-liposomes without PrK in serum-containing medium. LN-PrK-siRNA complexes showed increased stability in serum and reduced toxicity in KB cells relative to LN-siRNA complexes.

CONCLUSION: LN-PrK-siRNA complexes are promising delivery vehicles for siRNA.

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