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学科主题: 药学
题名:
A novel gemini-like cationic lipid for the efficient delivery of siRNA
作者: Zheng, Yi; Guo, Yujia; Li, Yating; Wu, Yun; Zhang, Lihe; Yang, Zhenjun
刊名: NEW JOURNAL OF CHEMISTRY
发表日期: 2014-10-01
DOI: 10.1039/c4nj00531g
卷: 38, 期:10, 页:4952-4962
收录类别: SCI ; IC
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Chemistry, Multidisciplinary
研究领域[WOS]: Chemistry
关键词[WOS]: CLINICAL-TRIALS WORLDWIDE ; GENE DELIVERY ; ANTISENSE OLIGONUCLEOTIDES ; TRANSFECTION PROPERTIES ; RNA INTERFERENCE ; MAMMALIAN-CELLS ; IN-VITRO ; NANOPARTICLES ; THERAPY ; DNA
英文摘要:

Although RNAi is a promising strategy for the intervention of human diseases, an essential prerequisite is the development of low-toxic and efficient siRNA delivery systems. In this report, we describe a novel gemini-like cationic lipid (CLD) that was developed and evaluated for the delivery of siRNA. The novel lipid contains a disulfide bond in the spacer, which can be cleaved under reductive conditions in the cytoplasm and decrease lipid toxicity. The liposomes formed by CLD exhibited a high siRNA binding property, which was facilitated by the increased number of cationic charges. Moreover, the cationic lipids showed tow cytotoxicity. They protected siRNAs from degradation by nucleases and the complexed siRNA was released efficiently in the presence of low concentrations of polyanionic heparin. High content screening and confocal microscopy studies demonstrated that lipoplexes with FAM labeled siRNA showed efficient cell uptake by HeLa and A375 cells. Finally, siRNA targeting MEK1 mRNA formulated in Liposomes demonstrated effective endosomal escape after cellular uptake and efficient gene silencing of MEK1 expression. These results demonstrated the promising use of the novel gemini-like cationic lipid for the efficient and safe delivery of siRNA.

语种: 英语
所属项目编号: 2012CB720604 ; 2012AA022501 ; 20932001
项目资助者: Ministry of Science and Technology of China (the National Key Basic Research Program of China) ; National Natural Science Foundation of China
WOS记录号: WOS:000342725800042
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66756
Appears in Collections:北京大学药学院_期刊论文

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作者单位: Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China

Recommended Citation:
Zheng, Yi,Guo, Yujia,Li, Yating,et al. A novel gemini-like cationic lipid for the efficient delivery of siRNA[J]. NEW JOURNAL OF CHEMISTRY,2014,38(10):4952-4962.
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