title: The application of pH-sensitive polymer-lipids to antigen delivery for cancer immunotherapy.
abstract: For production of pH-sensitive liposomes, we developed pH-sensitive polymer-lipids that consists of pH-sensitive fusogenic polymer moieties such as 3-methyl glutarylated poly(glycidol) and 2-carboxycyclohexane-1-carboxylated poly(glycidol), connected to a phosphatidylethanolamine head group. Incorporation of these pH-sensitive polymer-lipids into egg yolk phosphatidylcholine liposomes produced highly pH-sensitive liposomes that were stable at neutral pH but which destabilized markedly in response to very small pH change in weakly acidic pH region. These liposomes delivered their contents (pyranine) into cytosol of dendritic cell-derived DC2.4 cells. When these polymer-lipid-incorporated liposomes loaded with antigenic protein ovalbumin (OVA) were administered subcutaneously to mice, the antigen-specific cellular immunity was induced efficiently in the mice. Furthermore, immunization of mice with these OVA-loaded pH-sensitive polymer-lipid-incorporated liposomes induced strong OVA-specific immunity, which achieved complete rejection of OVA-expressing E.G7-OVA cells and marked regression of E.G7-OVA tumors.
authors: Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
authors: Eiji
authors: E
authors: Yuba
authors: Yoshikazu
authors: Y
authors: Kono
authors: Atsushi
authors: A
authors: Harada
authors: Shoichi
authors: S
authors: Yokoyama
authors: Masaya
authors: M
authors: Arai
authors: Kazuhiro
authors: K
authors: Kubo
authors: Kenji
authors: K
authors: Kono
mesh_terms: D000818:Animals; D000941:Antigens; D001190:Arylsulfonates / Q000737:chemistry; D002460:Cell Line; D005260:Female; D006863:Hydrogen-Ion Concentration; D007109:Immunity; D007114:Immunization; D007167:Immunotherapy / Q000379:methods*; D008055:Lipids / Q000138:chemical synthesis / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D010047:Ovalbumin / Q000276:immunology; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010799:Phycoerythrin / Q000378:metabolism; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D012235:Rhodamines / Q000378:metabolism; D013696:Temperature
chemical_list: D000941:Antigens; D001190:Arylsulfonates; D008055:Lipids; D008081:Liposomes; D010714:Phosphatidylethanolamines; D011108:Polymers; D012235:Rhodamines; D010799:Phycoerythrin; C038089:1,2-distearoylphosphatidylethanolamine; D010047:Ovalbumin; C005047:pyranine