title: Liver cell specific targeting by the preS1 domain of hepatitis B virus surface antigen displayed on protein nanocages.
abstract: Protein nanocages are self-organized complexes of oligomers whose three-dimensional architecture can been determined in detail. These structures possess nanoscale inner cavities into which a variety of molecules, including therapeutic or diagnostic agents, can be encapsulated. These properties yield these particles suitable for a new class of drug delivery carrier, or as a bioimaging reagent that might respond to biochemical signals in many different cellular processes. We report here the design, synthesis, and biological characterization of a hepatocyte-specific nanocage carrying small heat-shock protein. These nanoscale protein cages, with a targeting peptide composed of a preS1 derivative from the hepatitis B virus on their surfaces, were prepared by genetic engineering techniques. PreS1-carrying nanocages showed lower cytotoxicity and significantly higher specificity for human hepatocyte cell lines than other cell lines in vitro. These results suggested that small heat-shock protein-based nanocages present great potential for the development of effective targeted delivery of various agents to specific cells.
authors.affiliation: Department of Advanced Medical Initiatives, Faculty of Medical Science, Kyushu University, Fukuoka, Japan. m-murata@dem.med.kyushu-u.ac.jp
authors.forename: Masaharu
authors.initials: M
authors.lastname: Murata
authors.forename: Sayoko
authors.initials: S
authors.lastname: Narahara
authors.forename: Kaori
authors.initials: K
authors.lastname: Umezaki
authors.forename: Riki
authors.initials: R
authors.lastname: Toita
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Tabata
authors.forename: Jing Shu
authors.initials: JS
authors.lastname: Piao
authors.forename: Kana
authors.initials: K
authors.lastname: Abe
authors.forename: Jeong-Hun
authors.initials: JH
authors.lastname: Kang
authors.forename: Kenoki
authors.initials: K
authors.lastname: Ohuchida
authors.forename: Lin
authors.initials: L
authors.lastname: Cui
authors.forename: Makoto
authors.initials: M
authors.lastname: Hashizume
mesh_terms: D002470:Cell Survival / Q000502:physiology; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D006514:Hepatitis B Surface Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D018613:Microscopy, Confocal; D053769:Nanocapsules / Q000737:chemistry*; D050997:Nanomedicine; D010316:Particle Size; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D006360:Heat-Shock Proteins; D006514:Hepatitis B Surface Antigens; D053769:Nanocapsules; D011498:Protein Precursors; D011993:Recombinant Fusion Proteins; C050806:presurface protein 1, hepatitis B surface antigen