小干扰RNA
转染
分子生物学
胰腺癌
基因沉默
体内
癌症研究
基因敲除
化学
生物
细胞培养
癌症
生物化学
基因
遗传学
生物技术
作者
Linjuan Zeng,Jingguo Li,Jiajia Li,Qiubo Zhang,Chenchen Qian,Wei Wu,Zhong Lin,Jianzhong Liang,Yinting Chen,Kaihong Huang
出处
期刊:Pancreas
[Ovid Technologies (Wolters Kluwer)]
日期:2015-03-01
卷期号:44 (2): 250-259
被引量:13
标识
DOI:10.1097/mpa.0000000000000241
摘要
The objective of this study was to establish an efficient carrier for small interfering RNA (siRNA) delivery targeting pancreatic tumor cells.A copolymer consisting of a single-chain variable fragment targeted to human CD44 variant 6 (scFv(CD44v6)) 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.The scFv(CD44v6) 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.The scFv(CD44v6)-conjugated nanocarriers provide a highly efficient and safe platform for systemic gene therapy for pancreatic cancer.
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