title: Dextran derivative-based pH-sensitive liposomes for cancer immunotherapy.
abstract: pH-Sensitive dextran derivatives having 3-methylglutarylated residues (MGlu-Dex) were prepared by reacting dextran with 3-methyl-glutaric anhydride. MGlu-Dex changed the protonation state and their characteristics from hydrophilic to hydrophobic in neutral and acidic pH regions. Surface modification of egg yolk phosphatidylcholine liposomes with MGlu-Dex produced highly pH-sensitive liposomes that were stable at neutral pH but which were destabilized strongly in the weakly acidic pH region. MGlu-Dex-modified liposomes were taken up efficiently by dendritic cells and delivered entrapped ovalbumin (OVA) molecules into the cytosol. When MGlu-Dex-modified liposomes loaded with OVA were administered subcutaneously to mice, the antigen-specific humoral and cellular immunity was induced more effectively than the unmodified liposomes loaded with OVA. Furthermore, administration of MGlu-Dex-modified liposomes loaded with OVA to mice bearing E.G7-OVA tumor significantly suppressed tumor growth and extended the mice survival. Results suggest that MGlu-Dex-modified liposomes are promising for the production of safe and potent antigen delivery systems that contribute to the establishment of efficient cancer immunotherapy.
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: yuba@chem.osakafu-u.ac.jp.
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: Naoki
authors.initials: N
authors.lastname: Tajima
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: Atsushi
authors.initials: A
authors.lastname: Harada
authors.affiliation: Science Lin, 1-1-35, Nishiawaji, Higashiyodogawa-ku, Osaka, Osaka 533-0031, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hayashi
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: D000812:Anhydrides / Q000138:chemical synthesis / Q000737:chemistry; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D002460:Cell Line; D011232:Chemical Precipitation; D003911:Dextrans / Q000138:chemical synthesis / Q000737:chemistry*; D005260:Female; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000378:metabolism; D005977:Glutarates / Q000138:chemical synthesis / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007109:Immunity; D007114:Immunization; D007167:Immunotherapy; D007371:Interferon-gamma / Q000096:biosynthesis; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D010047:Ovalbumin / Q000378:metabolism; D010316:Particle Size; D011721:Pyrenes / Q000737:chemistry; D055672:Static Electricity; D040521:Subcutaneous Tissue / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D017186:Titrimetry
chemical_list: D000812:Anhydrides; D000951:Antigens, Neoplasm; D003911:Dextrans; D005456:Fluorescent Dyes; D005977:Glutarates; D008081:Liposomes; D011721:Pyrenes; C079643:glutaric anhydride; D007371:Interferon-gamma; D010047:Ovalbumin; C030984:pyrene
keywords: Cancer immunotherapy; Cellular immunity; Cytoplasmic delivery; Dendritic cell; Dextran; pH-Sensitive liposome