Abstract 5710: Effective siRNA delivery through specific targeting of tumor

Abstract

Abstract The siRNA has been expected to apply for several diseases such as cancer since siRNA specifically silences the disease-associated genes. However, effective gene carriers should be developed to overcome the low siRNA stability in vivo, form stable complexes and facilitate intracellular uptake of siRNA. Here, we have investigated tumor targetable oligopeptide carrier including tumor-homing peptide, AP-1, and rich positive peptide, nine arginines, for systemic siRNA delivery. Phage display technique is a promising tool for selecting peptides or proteins with specific binding properties from a lot of variants. AP-1 peptide can bind with interleukin-4 receptor which expressed on surface of several human cancer cells like MDA-MB231. Arginine rich peptides have been widely used for forming complex with DNA, which promote efficient transfection in various mammalian cells. Oligopeptides formed ionic complex with siRNA at 150 nm size and these peptide/siRNA complexes were transfected in MDA-MB231. Under in vitro silencing experiments, peptide/siRNA complexes did silencing of Dronpa gene as similar to lipofectamine/siRNA complexes, which were observed by fluorescent microscope, flow cytometry, and western blotting analysis. For in vivo experiments, we prepared tumorbearing mice by inoculation of Dronpa-MDA-MB231 cells (Dronpa-stable cells). Tumor targetable oligopeptide/siRNA complexes were administrated through tale vein when tumor volume reached at 50 mm3 - we observed fluorescent signals of Dronpa in tumor. In tumor targetable oligopeptide/siRNA-treated mice, weak signals of Dronpa were observed compared with free siRNA-treated mice. These results revealed the promising potential of our oligopeptide carrier as a stable and effective siRNA delivery system for cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5710. doi:1538-7445.AM2012-5710