title: Construction of an improved drug delivery system tool with enhanced versatility in cell-targeting.
abstract: OBJECTIVE
  The aim of this study was to develop an improved drug delivery system (DDS) tool with enhanced versatility in the cell-targeting step using as Z-domain, a modified IgG binding domain of protein A from Staphylococcus aureus, as an IgG adapter domain.
  
  
  METHODS
  The chimera protein expression system composed of the Z-domain and chimeric cholesterol-dependent cytolysin mutant named His-Z-CDC(ss)(IS) was constructed in Escherichia coli. His-Z-CDC(ss)(IS) was purified by Ni-affinity chromatography, and its abilities for controlled pore formation, membrane binding, IgG binding, and target cell-specific delivery of liposomes carrying medicine were investigated.
  
  
  CONCLUSIONS
  His-Z-CDC(ss)(IS) purified by Ni-affinity chromatography indicated pore-forming activity only under disulfide bond reducing conditions. His-Z-CDC(ss)(IS) also demonstrated an ability to bind both IgG and cholesterol-embedded liposomes via its Z-domain and domain 4, respectively. Furthermore, anticarcinoembryonic antigen (CEA) IgG-bound His-Z-CDC(ss)(IS) indicated effective delivery of liposomes carrying drugs to CEA-expressing cells.
  
  
  CONCLUSIONS
  His-Z-CDC(ss)(IS) was revealed to be an improved DDS tool with enhanced versatility in cell targeting.
authors.affiliation: Department of Biological Science and Technology, Institute of Technology and Science, Graduate School, University of Tokushima, Tokushima, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tabata
authors.forename: Yukimasa
authors.initials: Y
authors.lastname: Ohkubo
authors.forename: Masato
authors.initials: M
authors.lastname: Tamura
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tomoyasu
authors.forename: Kazuto
authors.initials: K
authors.lastname: Ohkura
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nagamune
mesh_terms: D002272:Carcinoembryonic Antigen / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D016503:Drug Delivery Systems; D005347:Fibroblasts / Q000378:metabolism*; D005472:Fluorouracil / Q000008:administration & dosage; D006461:Hemolysis / Q000187:drug effects; D056945:Hep G2 Cells / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008081:Liposomes; D054353:Perforin / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism*; D013211:Staphylococcus aureus
chemical_list: D002272:Carcinoembryonic Antigen; D007074:Immunoglobulin G; D008081:Liposomes; D011993:Recombinant Fusion Proteins; D054353:Perforin; D002784:Cholesterol; D005472:Fluorouracil
keywords: Cholesterol-dependent cytolysin; Z-domain; chimera protein; drug delivery system