title: A nanocarrier system for the delivery of nucleic acids targeted to a pancreatic beta cell line.
abstract: Pancreatic β cells secrete insulin in response to glucose levels and thus are involved in controlling blood glucose levels. A line of pancreatic β cells "MIN6" has been used in studies related to the function of β cells and diabetes therapy. Regulating gene expression in MIN6 cells could accelerate these studies, but an efficient method for the transfection of nucleic acids targeted to MIN6 cells is required. We report here on a liposome-based carrier targeted to pancreatic β cells (Multifunctional envelope-type nano device for pancreatic β cells, β-MEND). We identified a lipid composition for use in preparing the β-MEND, which permits the particles to be efficiently internalized into MIN6, as evidenced by flow cytometry analyses. Intracellular observation by confocal laser scanning microscopy showed that the β-MEND efficiently delivered the oligo nucleic acids to the cytosol of MIN6 cells. Moreover, using a β-MEND encapsulating a 2'-O-Methyl RNA complementary to a microRNA that suppresses insulin secretion, the knockdown of the targeted microRNA and an up-regulation of insulin secretion were observed in MIN6. Thus, the β-MEND holds promise as an efficient system for delivering nucleic acids targeted to MIN6 and can contribute to research and therapy aimed at diabetes.
authors.affiliation: Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Yuma
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Tabata
authors.affiliation: Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Yasuzaki
authors.affiliation: Department of Endocrine and Metabolic Diseases/Diabetes Mellitus, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Nomura
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shibata
authors.affiliation: Department of Endocrine and Metabolic Diseases/Diabetes Mellitus, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Ibayashi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Taniguchi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sasaki
authors.affiliation: Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan. Electronic address: harasima@pharm.hokudai.ac.jp.
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects; D055785:Gene Knockdown Techniques; D018014:Gene Transfer Techniques; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008055:Lipids / Q000737:chemistry; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D009696:Nucleic Acids / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D014162:Transfection
chemical_list: D007328:Insulin; D008055:Lipids; D035683:MicroRNAs; C540349:Mirn375 microRNA, mouse; D009696:Nucleic Acids; D016376:Oligonucleotides, Antisense; D005947:Glucose
keywords: Diabetes; MIN6 cell; Multifunctional envelope-type nano device (MEND); Nucleic acids delivery; Pancreatic β cells; microRNA