title: A liposome-based antigen delivery system using pH-sensitive fusogenic polymers for cancer immunotherapy.
abstract: Highly pH-sensitive liposomes that deliver antigenic molecules into cytosol through fusion with or destabilization of endosome were prepared by surface modification of egg yolk phosphatidylcholine/dioleoylphosphatidylethanolamine (1/1, mol/mol) liposomes with 3-methylglutarylated poly(glycidol) of linear (MGlu-LPG) or hyperbranched structure (MGlu-HPG). These polymer-modified liposomes were stable at neutral pH, but they became strongly destabilized below pH 6, which corresponds to the pH of endosome. These polymer-modified liposomes were taken up by murine dendritic cells (DCs) more efficiently than the unmodified liposomes were through an endocytic pathway. They introduced entrapped ovalbumin (OVA) molecules into cytosol. Subcutaneous or nasal administration of the polymer-modified liposomes loaded with OVA induced generation of OVA-specific cytotoxic T cells (CTL) much more effectively than the unmodified liposomes loaded with OVA. Furthermore, administration of the polymer-modified OVA-loaded liposomes to mice bearing E.G7-OVA tumor significantly reduced the tumor burden, although the OVA-loaded unmodified liposomes only slightly affected tumor growth. Results suggest that the polymer-modified liposomes with highly pH-sensitive destabilizing property are promising as antigen carriers for efficient cancer immunotherapy.
authors: Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, Sakai, Osaka, Japan. yuba@chem.osakafu-u.ac.jp
authors: Eiji
authors: E
authors: Yuba
authors: Atsushi
authors: A
authors: Harada
authors: Yuichi
authors: Y
authors: Sakanishi
authors: Shinobu
authors: S
authors: Watarai
authors: Kenji
authors: K
authors: Kono
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D006863:Hydrogen-Ion Concentration; D007167:Immunotherapy; D008081:Liposomes; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D010047:Ovalbumin / Q000008:administration & dosage*; D011108:Polymers / Q000008:administration & dosage*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D008081:Liposomes; D011108:Polymers; D010047:Ovalbumin