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Application of apolipoprotein E-modified liposomal nanoparticles as a carrier for delivering DNA and nucleic acid in the brain

International Journal of Nanomedicine. 2014;2014(Issue 1):4267-4276

 

Journal Homepage

Journal Title: International Journal of Nanomedicine

ISSN: 1176-9114 (Print); 1178-2013 (Online)

Publisher: Dove Medical Press

LCC Subject Category: Medicine: Medicine (General)

Country of publisher: United Kingdom

Language of fulltext: English

 

AUTHORS


Tamaru M

Akita H

Nakatani T

Kajimoto K

Sato Y

Hatakeyama H

Harashima H

EDITORIAL INFORMATION

 

Abstract | Full Text

Mina Tamaru,* Hidetaka Akita,* Taichi Nakatani, Kazuaki Kajimoto, Yusuke Sato, Hiroto Hatakeyama, Hideyoshi Harashima Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan *These authors contributed equally to this work Abstract: An innovative drug delivery technology is urgently needed to satisfy unmet medical needs in treating various brain disorders. As a fundamental carrier for plasmid DNA or nucleic acids, we developed a liposomal nanoparticle (multifunctional envelope-type nano device [MEND]) containing a proton-ionizable amino lipid (YSK-MEND). Here we report on the impact of apolipoprotein E (ApoE) modification on the function of YSK-MEND in terms of targeting brain cells. The cellular uptake and function of YSK-MEND encapsulating short interference RNA or plasmid DNA were significantly improved as a result of ApoE modification in mouse neuron-derived cell lines (Neuro-2a and CAD). Intracerebroventricular administration of ApoE-modified YSK-MEND (ApoE/YSK-MEND) encapsulating plasmid DNA also resulted in higher transgene expression in comparison with YSK-MEND that was not modified with ApoE. Moreover, observation of fluorescence-labeled ApoE/YSK-MEND and expression of mCherry (fluorescence protein) derived from plasmid DNA indicated that this carrier might be useful for delivering and conferring transgene expression in neural stem cells and/or neural progenitor cells. Thus, this system may be a useful tool for the treatment of neurodegenerative disease. Keywords: brain, DNA, oligonucleotide, delivery, nanoparticles