title: Application of apolipoprotein E-modified liposomal nanoparticles as a carrier for delivering DNA and nucleic acid in the brain.
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.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Mina
authors.initials: M
authors.lastname: Tamaru
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Akita
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Nakatani
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Kajimoto
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Hatakeyama
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000737:chemistry*; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002460:Cell Line; D004247:DNA / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics*; D008081:Liposomes / Q000737:chemistry* / Q000493:pharmacokinetics; D008164:Luminescent Proteins / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000737:chemistry*; D009696:Nucleic Acids / Q000737:chemistry / Q000493:pharmacokinetics; D010316:Particle Size; D014162:Transfection / Q000379:methods; D000097573:Red Fluorescent Protein
chemical_list: D001057:Apolipoproteins E; D004247:DNA; D004337:Drug Carriers; D008081:Liposomes; D008164:Luminescent Proteins; D009696:Nucleic Acids; D000097573:Red Fluorescent Protein
keywords: DNA; brain; delivery; nanoparticles; oligonucleotide