title: An apolipoprotein E modified liposomal nanoparticle: ligand dependent efficiency as a siRNA delivery carrier for mouse-derived brain endothelial cells.
abstract: A disorder in the brain endothelium is thought to be closely related to the pathophysiology of brain diseases. A method for delivering nucleic acids (i.e. short interference RNA; siRNA) to the brain endothelium should be an attractive strategy for curing brain disorders. A liposomal nanoparticle containing a proton-ionizable amino lipid was recently developed as a carrier of encapsulated siRNA. The aim of this study was to evaluate the utility of apolipoprotein E (ApoE) as a targeting ligand for mouse brain endothelial cells (MBEC4 cells). The cellular uptake of the ApoE-modified nanoparticles was gradually increased in an ApoE-density dependent manner. Furthermore, the ApoE-modified nanoparticles were taken up via both clathrin and caveolae mediated endocytosis, thus permitting them to avoid lysosomal degradation. Finally, endogenous gene silencing in MBEC4 cells was efficiently achieved depending on the ApoE-modification. Collectively, the ApoE-modified nanoparticle is a promising carrier for delivering nucleic acids to the brain endothelium.
authors: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors: Mina
authors: M
authors: Tamaru
authors: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan. Electronic address: akita@pharm.hokudai.ac.jp.
authors: Hidetaka
authors: H
authors: Akita
authors: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors: Kazuaki
authors: K
authors: Kajimoto
authors: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors: Yusuke
authors: Y
authors: Sato
authors: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors: Hiroto
authors: H
authors: Hatakeyama
authors: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan. Electronic address: harasima@pharm.hokudai.ac.jp.
authors: Hideyoshi
authors: H
authors: Harashima
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D001921:Brain / Q000098:blood supply*; D021941:Caveolae / Q000378:metabolism; D002460:Cell Line; D022163:Clathrin-Coated Vesicles / Q000378:metabolism; D004705:Endocytosis; D042783:Endothelial Cells / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D008055:Lipids; D008081:Liposomes; D051379:Mice; D053758:Nanoparticles; D010880:Piperidines / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism*; D014162:Transfection / Q000379:methods*
chemical_list: D001057:Apolipoproteins E; D008055:Lipids; D008081:Liposomes; D010880:Piperidines; D034741:RNA, Small Interfering; C580570:YSK05; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases
keywords: Apolipoprotein E (ApoE); Brain endothelial cell; In vitro; Multifunctional envelope-type nano device (MEND); YSK05; siRNA delivery