title: pH-sensitive polymer-liposome-based antigen delivery systems potentiated with interferon-γ gene lipoplex for efficient cancer immunotherapy.
abstract: Potentiation of pH-sensitive liposome-based antigen carriers with IFN-γ gene lipoplexes was attempted to achieve efficient induction of tumor-specific immunity. 3-Methylglutarylated poly(glycidol) (MGluPG)-modified liposomes and cationic liposomes were used, respectively, for the delivery of antigenic protein ovalbumin (OVA) and IFN-γ-encoding plasmid DNA (pDNA). The MGluPG-modified liposomes and the cationic liposome-pDNA complexes (lipoplexes) formed hybrid complexes via electrostatic interactions after their mixing in aqueous solutions. The hybrid complexes co-delivered OVA and IFN-γ-encoding pDNA into DC2.4 cells, a murine dendritic cell line, as was the case of MGluPG-modified liposomes for OVA or the lipoplexes for pDNA. Both the lipoplexes and the hybrid complexes transfected DC2.4 cells and induced IFN-γ protein production, but transfection activities of the hybrid complexes were lower than those of the parent lipoplexes. Subcutaneous administration of hybrid complexes to mice bearing E.G7-OVA tumor reduced tumor volumes, which might result from the induction of OVA-specific cytotoxic T lymphocytes (CTLs). However, the hybrid complex-induced antitumor effect was the same level of the MGluPG-modified liposome-mediated antitumor immunity. In contrast, an extremely strong antitumor immune response was derived when these liposomes and lipoplexes without complexation were injected subcutaneously at the same site of tumor-bearing mice. Immunohistochemical analysis of tumor sections revealed that immunization through the liposome-lipoplex combination promoted the infiltration of CTLs to tumors at an early stage of treatment compared with liposomes, resulting in strong therapeutic effects.
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Yuba
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Kanda
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Yoshizaki
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
authors.forename: Ryoma
authors.initials: R
authors.lastname: Teranishi
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Harada
authors.affiliation: Division of Veterinary Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58 Rinku-oraikita, Izumisano, Osaka 598-8531, Japan.
authors.forename: Kikuya
authors.initials: K
authors.lastname: Sugiura
authors.affiliation: Division of Veterinary Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58 Rinku-oraikita, Izumisano, Osaka 598-8531, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Izawa
authors.affiliation: Division of Veterinary Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58 Rinku-oraikita, Izumisano, Osaka 598-8531, Japan.
authors.forename: Jyoji
authors.initials: J
authors.lastname: Yamate
authors.affiliation: Terumo Corp., Ltd., Ashigarakami-gun, Kanagawa 259-0151, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Sakaguchi
authors.affiliation: Terumo Corp., Ltd., Ashigarakami-gun, Kanagawa 259-0151, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Koiwai
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan. Electronic address: kono@chem.osakafu-u.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kono
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D045744:Cell Line, Tumor; D003712:Dendrites / Q000378:metabolism; D016503:Drug Delivery Systems; D004586:Electrophoresis; D005260:Female; D005455:Fluorescent Antibody Technique; D006863:Hydrogen-Ion Concentration; D007167:Immunotherapy; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics*; D008081:Liposomes / Q000737:chemistry; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D010047:Ovalbumin / Q000276:immunology; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D011409:Propylene Glycols / Q000737:chemistry; D013154:Spleen / Q000276:immunology; D055672:Static Electricity; D040521:Subcutaneous Tissue; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000941:Antigens; D008081:Liposomes; D011108:Polymers; D011409:Propylene Glycols; C502907:polyglycidol; D007371:Interferon-gamma; D010047:Ovalbumin
keywords: Cancer immunotherapy; Cellular immunity; Dendritic cell; Interferon-γ; Lipoplex; pH-sensitive liposome