title: Expression and characterization of myristoylated preS1-conjugated nanocages for targeted cell delivery.
abstract: Lipid modification of proteins plays key roles in cellular signaling pathways. We describe the development of myristoylated preS1-nanocages (myr-preS1-nanocages) that specifically target human hepatocyte-like HepaRG cells in which a specific receptor-binding peptide (preS1) is joined to the surface of naturally occurring ferritin cages. Using a genetic engineering approach, the preS1 peptide was joined to the N-terminal regions of the ferritin cage via flexible linker moieties. Myristoylation of the preS1 peptide was achieved by co-expression with yeast N-myristoyltransferase-1 in the presence of myristic acid in Escherichia coli cells. The myristoylated preS1-nanocages exhibited significantly greater specificity for human hepatocyte-like HepaRG cells than the unmyristoylated preS1-nanocages. These results suggest that the lipid-modified nanocages have great potential for effective targeted delivery to specific cells.
authors.affiliation: Department of Advanced Medical Initiatives, Faculty of Medical Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: m-murata@dem.med.kyushu-u.ac.jp.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Murata
authors.affiliation: Department of Advanced Medical Initiatives, Faculty of Medical Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Jing Shu
authors.initials: JS
authors.lastname: Piao
authors.affiliation: Department of Advanced Medical Initiatives, Faculty of Medical Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Sayoko
authors.initials: S
authors.lastname: Narahara
authors.affiliation: Department of Advanced Medical Initiatives, Faculty of Medical Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Takahito
authors.initials: T
authors.lastname: Kawano
authors.affiliation: Department of Advanced Medical Initiatives, Faculty of Medical Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Hamano
authors.affiliation: Department of Biomedical Engineering, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan.
authors.forename: Jeong-Hun
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Department of Microbiology, St. Marianna University School of Medicine, Sugao 2-16-1 Miyamae, Kawasaki 216-8511, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Asai
authors.affiliation: Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Ugawa
authors.affiliation: Department of Advanced Medical Initiatives, Faculty of Medical Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hashizume
mesh_terms: D000217:Acyltransferases / Q000737:chemistry / Q000235:genetics; D002460:Cell Line; D003001:Cloning, Molecular; D016503:Drug Delivery Systems; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005293:Ferritins / Q000737:chemistry / Q000235:genetics*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics; D015870:Gene Expression; D005818:Genetic Engineering; D006514:Hepatitis B Surface Antigens / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification; D022781:Hepatocytes / Q000737:chemistry* / Q000473:pathology / Q000821:virology; D006801:Humans; D058990:Molecular Targeted Therapy; D019814:Myristic Acid / Q000737:chemistry / Q000378:metabolism; D010957:Plasmids / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification
chemical_list: D005656:Fungal Proteins; D006514:Hepatitis B Surface Antigens; D011498:Protein Precursors; D011991:Receptors, Virus; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C050806:presurface protein 1, hepatitis B surface antigen; D019814:Myristic Acid; D005293:Ferritins; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase
keywords: Ferritin; Hepatitis B virus; Myristoylation; Protein cage; Targeted delivery