期刊论文详细信息
Drug Delivery
DOTAP functionalizing single-walled carbon nanotubes as non-viral vectors for efficient intracellular siRNA delivery
Lei Wang1  Zhenzhong Zhang1  Yali Wang1  Shasha Jia1  Haixia Li1  Lijia Yang1  Yun Zhang1  Yongwei Hao1  Ning Wang2 
[1] School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450002, China;School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450002, China;Department of pharmacy, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, Chin;
关键词: Cancer therapy;    gene silencing;    non-viral vector;    single-walled carbon nanotubes;    siRNA;   
DOI  :  10.3109/10717544.2014.919542
来源: publisher
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【 摘 要 】

Context: Functionalized single-walled carbon nanotubes (SWNT) with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) were used as novel and more convenient carriers of small interfering RNA (siRNA).Objective: To utilize the unique capability of SWNT to be easily modified by functional groups and readily internalized by mammalian cells to bind, condense, stabilize siRNA and enhance its transfection efficiency.Methods: After SWNT were non-covalently functionalized by cationic DOTAP (SWNT–DOTAP), siRNA interacted with SWNT–DOTAP via static electricity (SWNT–DOTAP/siRNA). Subsequently, the size, zeta potential and morphology of SWNT–DOTAP/siRNA were analyzed. The optimal compression ratio and stability of siRNA were assessed by agarose gel electrophoresis. Furthermore, in prostate carcinoma PC-3 cells, RT-PCR, flow cytometry and sulforhodamine B assays were used to evaluate the silencing activity, transfection efficiency and cell proliferation, respectively.Results and discussion: The characteristics of SWNT–DOTAP, i.e. an average size of 194.49 nm, a zeta potential of 45.16 mV and lower cytotoxicity than Lipofectamine 2000, indicated that this vector was suitable for siRNA delivery. Moreover, after interaction with SWNT–DOTAP, siRNA of human telomerase reverse transcriptase was bound, condensed and stabilized. In PC-3 cells, SWNT–DOTAP/siRNA exhibited 82.6% silencing activity and 92% transfection efficiency. Furthermore, the complexes inhibited cell proliferation by 42.1%.Conclusion: SWNT–DOTAP may be a promising siRNA delivery vector for gene-based therapeutic applications in cancer.

【 授权许可】

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