Suppression of tumor growth in lung cancer xenograft model mice by poly(sorbitol-co-PEI)-mediated delivery of osteopontin siRNA.

Abstract

Small interfering RNA (siRNA)-mediated gene silencing represents a promising strategy for treating diseases such as cancer; however, specific gene silencing requires an effective delivery system to overcome the instability and low transfection efficiency of siRNAs. To address this issue, a polysorbitol-based transporter (PSOT) was prepared by low molecular weight branched polyethylenimine (bPEI) crosslinked with sorbitol diacrylate (SDA). Osteopontin (OPN) gene, which is highly associated with non-small cell lung cancer (NSCLC) was targeted by siRNA therapy using siRNA targeting OPN (siOPN). Characterization study confirmed that PSOT formed compact complexes with siOPN and protected siOPN against degradation by RNase. PSOT/siOPN complexes demonstrated low cytotoxicity and enhanced transfection efficiency in vitro, suggesting that this carrier may be suitable for gene silencing. In the A549 and H460 lung cancer cell lines, PSOT/siOPN complexes demonstrated significant silencing efficiency at both RNA and protein levels. To study in vivo tumor growth suppression, two lung cancer cell-xenograft mouse models were prepared and PSOT/siOPN complexes were delivered into the mice through intravenous injection. The siOPN-treated groups demonstrated significantly reduced OPN expression at both the RNA and protein levels as well as suppression of tumor volume and weight. Taken together, siOPN delivery using PSOT may present an effective and novel therapeutic system for lung cancer treatment.

• Authors: Won-Young Cho, Seong-Ho Hong, Bijay Singh, Mohammad Ariful Islam, Somin Lee, Ah Young Lee, Nomundelger Gankhuyag, Ji-Eun Kim, Kyeong-Nam Yu, Kwang-Ho Kim, Young-Chan Park, Chong-Su Cho, Myung-Haing Cho
• Journal: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V (Eur J Pharm Biopharm) Vol. 94 Pg. 450-62 (Aug 2015) ISSN: 1873-3441 [Electronic] Netherlands
• PMID: 26141346 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Drug Carriers
• RNA, Small Interfering
• Spp1 protein, mouse
• Osteopontin
• Sorbitol
• Polyethyleneimine

Topics

• Animals
• Blotting, Western
• Cell Line, Tumor
• Drug Carriers (chemistry)
• Gene Expression
• Gene Silencing
• Gene Transfer Techniques
• Humans
• Lung Neoplasms (genetics, pathology, therapy)
• Male
• Mice, Inbred BALB C
• Mice, Nude
• Osteopontin (genetics)
• Polyethyleneimine (chemistry)
• RNA, Small Interfering (administration & dosage, genetics)
• Real-Time Polymerase Chain Reaction
• Sorbitol (chemistry)
• Transfection
• Xenograft Model Antitumor Assays