Effective Suppression of the Kirsten Rat Sarcoma Viral Oncogene in Pancreatic Tumor Cells via Targeted Small Interfering RNA Delivery Using Nanoparticles. Issue 2 (March 2015)

• Record Type: Journal Article
• Authors: Zeng, Linjuan; Li, Jingguo; Li, Jiajia; Zhang, Qiubo; Qian, Chenchen; Wu, Wei; Lin, Zhong; Liang, Jianzhong; Chen, Yinting; Huang, Kaihong
• Is Part Of: Pancreas. Volume 44:Issue 2(2015)
• Publication Date: 2015-03
• Subjects: pancreatic tumor -- nanoparticles -- tumor targeting -- small interfering RNA -- CD44 variant 6 -- in vivo imaging; Pancreas -- Diseases -- Periodicals; Pancreas -- Periodicals; Neuroendocrine tumors -- Periodicals; 616.37005
• DOI: 10.1097/MPA.0000000000000241
• Languages: English
• ISSNs: 0885-3177

Abstract

Abstract : Objectives: The objective of this study was to establish an efficient carrier for small interfering RNA (siRNA) delivery targeting pancreatic tumor cells. Methods: A copolymer consisting of a single-chain variable fragment targeted to human CD44 variant 6 (scFvCD44v6 ) functional group conjugated to polyethylene glycol-poly-L-lysine was synthesized and assembled into micelles encapsulating the siRNAs. Flow cytometry and Western blot assays were performed to evaluate the transfection efficiency and gene-silencing effect of the siRNAs. Afterward, (4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide, Transwell, soft agar colony formation, and enzyme-linked immunosorbent assays were performed to evaluate the biological functions of PANC-1 cells after Kirsten rat sarcoma viral oncogene knockdown. In vivo assays were performed using a BALB/c (nu/nu) mouse model subcutaneously injected with PANC-1 xenografts. Real-time in vivo fluorescence imaging was used to monitor the tumor homing of the nanoparticles. Results: The scFvCD44v6 enabled more efficient delivery of siRNAs and exhibited enhanced gene silencing compared with nontargeted nanoparticles. Furthermore, targeted delivery of the siRNAs induced a potent inhibitory effect on cell proliferation, colony formation, invasion, and vascular endothelial growth factor production. The animal assays revealed that single-chain variable fragment nanoparticles accumulated in the tumor tissue and enhanced the inhibition of tumor growth in vivo. Conclusions: The scFvCD44v6 -conjugated nanocarriers provide a highly efficient and safe platform for systemic gene therapy for pancreatic cancer.