Suppression of tumor growth in xenograft model mice by small interfering RNA targeting osteopontin delivery using biocompatible poly(amino ester).

Abstract

Gene therapy using small interfering RNA (siRNA) is a novel strategy for effective anticancer therapies. However, low gene transfection efficiency and technical difficulties linked to siRNA delivery limit their practical application for gene delivery. Therefore, development of effective siRNA carriers is required. Overexpression of osteopontin (OPN) and its association with tumorigenesis has been reported in a majority of breast cancers. In this study, we used siRNA against OPN (siOPN) and investigated the possible OPN-dependent signaling pathway and the potential use of poly(amino ester) (PAE) based on glycerol propoxylate triacrylate (GPT) and spermine (SPE) for siRNA delivery. The GPT-SPE could effectively condense siRNA and protect the siRNA from RNaseA enzyme degradation. GPT-SPE/siRNA complexes showed good intracellular uptake and high gene silencing efficiency in vitro. Furthermore, in the breast cancer xenograft model, intratumoral injection of GPT-SPE/siOPN significantly inhibited tumor growth. These results demonstrated that silencing of OPN effectively suppressed the growth of breast cancer cells and further suggested that delivery of siRNA using GPT-SPE may act as an effective gene carrier for cancer therapy.

• Authors: Arash Minai-Tehrani, Hu-Lin Jiang, You-Kyoung Kim, Youn-Sun Chung, Kyeong-Nam Yu, Ji-Eun Kim, Ji-Young Shin, Seong-Ho Hong, Jae-Ho Lee, Hye-Joon Kim, Seung-Hee Chang, Sungjin Park, Bit Na Kang, Chong-Su Cho, Myung-Haing Cho
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 431 Issue 1-2 Pg. 197-203 (Jul 15 2012) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 22531848 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Acrylates
• Proliferating Cell Nuclear Antigen
• RNA, Small Interfering
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, mouse
• Fibroblast Growth Factor 2
• Osteopontin
• Spermine
• Matrix Metalloproteinase 9
• Mmp9 protein, mouse

Topics

• Acrylates (administration & dosage, chemistry)
• Animals
• Breast Neoplasms (metabolism, therapy)
• Cell Line, Tumor
• Fibroblast Growth Factor 2 (metabolism)
• Genetic Therapy
• Humans
• Matrix Metalloproteinase 9 (metabolism)
• Mice
• Mice, Nude
• Osteopontin (genetics, metabolism)
• Proliferating Cell Nuclear Antigen (metabolism)
• RNA, Small Interfering (administration & dosage, genetics)
• Spermine (administration & dosage, chemistry)
• Transfection (methods)
• Vascular Endothelial Growth Factor A (metabolism)
• Xenograft Model Antitumor Assays