首页 | 本学科首页   官方微博 | 高级检索  
     


Enhanced antisense efficacy of oligonucleotides adsorbed to monomethylaminoethylmethacrylate methylmethacrylate copolymer nanoparticles.
Authors:H P Zobel  M Junghans  V Maienschein  D Werner  M Gilbert  H Zimmermann  C Noe  J Kreuter  A Zimmer
Affiliation:1. Institut für Pharmazeutische Technologie, Biozentrum, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany;2. Institut für Pharmazeutische Chemie, Biozentrum, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany;3. Institut für Zoologie, Arbeitskreis Neurochemie, Biozentrum, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany;1. Institute of Chemical Engineering, Ningbo University of Technology, Ningbo 315016, China;2. Institute for Micromanufacturing, Louisiana Tech University, Ruston, Louisiana 71272, USA;3. Ural Federal University, Ekaterinburg 620002, Russia;1. State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Research Center for Analysis and Measurement & College of Materials Science and Engineering, Donghua University, Shanghai 201620, China;2. Research Institution for Biomimetics and Soft Matter, Fujian Key Provincial Laboratory for Soft Functional Materials Research, College of Materials, Xiamen University, 422 Siming Nan Road, Xiamen 361005, PR China;3. School of Chemistry, and Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China;1. Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China;2. Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China;1. Department of Physics, Zhejiang Normal University, Jinhua 321004, China;2. Department of Environmental Sciences, Zhejiang Normal University, Jinhua 321004, China;3. Department of Multi-media, Zhejiang Normal University, Jinhua 321004, China;4. College of Science, Shanghai Institute of Technology, Shanghai 200235, China
Abstract:The purpose of this study was the investigation of cationic nanoparticles as drug delivery systems for antisense oligonucleotides. Cationic monomethylaminoethylmethacrylate (MMAEMA) copolymer nanoparticles were prepared from N-monomethylaminoethylmethacrylate hydrochloride and methylmethacrylate. Oligonucleotides were adsorbed onto MMAEMA nanoparticles. Cell penetration was investigated in vitro with fluorescently labeled oligonucleotides and nanoparticles. Antisense effects of oligonucleotides adsorbed to MMAEMA nanoparticles were evaluated by sequence specific inhibition of ecto-5'-nucleotidase expression. The amount of enzyme expressed in PC12 cells was detected and quantified by immunocytochemistry using fluorescein isothiocyanate-labeled antibodies. Oligonucleotides were adsorbed to MMAEMA nanoparticles by the formation of ion-pairs between the positively charged secondary amino groups located on the particle surface and the anionic phosphodiester or phosphorothioate backbones of the oligonucleotides. Adsorption to nanoparticles led to an increased cellular uptake of oligonucleotides and to a significantly enhanced antisense efficacy of unmodified phosphodiester oligonucleotides as well as phosphorothioates. The results of the cell penetration and the antisense assay demonstrated that MMAEMA nanoparticles are promising carriers for oligonucleotide administration.
Keywords:
本文献已被 ScienceDirect 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号