ovalbumin and glutaric-anhydride

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.

Topics: Anhydrides; Animals; Antigens, Neoplasm; Cell Line; Chemical Precipitation; Dextrans; Female; Fluorescence; Fluorescent Dyes; Glutarates; Hydrogen-Ion Concentration; Immunity; Immunization; Immunotherapy; Interferon-gamma; Liposomes; Mice; Mice, Inbred C57BL; Neoplasms; Ovalbumin; Particle Size; Pyrenes; Static Electricity; Subcutaneous Tissue; T-Lymphocytes, Cytotoxic; Titrimetry