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  • 标题:siRNA Delivery into Tumor Cells by Cationic Cholesterol Derivative-Based Nanoparticles and Liposomes
  • 本地全文:下载
  • 作者:Yoshiyuki Hattori ; Eriko Hara ; Yumiko Shingu
  • 期刊名称:Biological and Pharmaceutical Bulletin
  • 印刷版ISSN:0918-6158
  • 电子版ISSN:1347-5215
  • 出版年度:2015
  • 卷号:38
  • 期号:1
  • 页码:30-38
  • DOI:10.1248/bpb.b14-00526
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要:

    Previously, we reported that cationic nanoparticles (NP) composed of diamine-type cholesteryl-3-carboxamide (OH-Chol, N -(2-(2-hydroxyethylamino)ethyl)cholesteryl-3-carboxamide) and Tween 80 could deliver small interfering RNA (siRNA) with high transfection efficiency into tumor cells. In this study, we synthesized new diamine-type cationic cholesteryl carbamate (OH-C-Chol, cholesteryl (2-((2-hydroxyethyl)amino)ethyl)carbamate) and triamine-type carbamate (OH-NC-Chol, cholesteryl (2-((2-((2-hydroxyethyl)amino)ethyl)amino)ethyl)carbamate), and prepared cationic nanoparticles composed of OH-C-Chol or OH-NC-Chol with Tween 80 (NP-C and NP-NC, respectively), as well as cationic liposomes composed of OH-C-Chol or OH-NC-Chol with 1,2-dioleoyl- sn -glycero-3-phosphoethanolamine (DOPE) (LP-C and LP-NC, respectively) for evaluation of their possible use as siRNA delivery vectors. LP-C and LP-NC/siRNA complexes (lipoplexes) exhibited larger gene silencing effects than NP-C and NP-NC/siRNA complexes (nanoplexes), respectively, in human breast tumor MCF-7 cells, although the NP-C nanoplex showed high association with the cells. In particular, LP-NC lipoplex could induce strong gene suppression, even at a concentration of 5 nM siRNA. From these results, cationic liposomes composed of OH-NC-Chol and DOPE may have potential as gene vectors for siRNA transfection to tumor cells.

  • 关键词:cationic nanoparticle; cationic liposome; small interfering RNA (siRNA) delivery; transfection; cholesteryl carbamate
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