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.
Subject(s)
Dextrans/chemistry , Immunotherapy , Liposomes/chemistry , Neoplasms/immunology , Neoplasms/therapy , Anhydrides/chemical synthesis , Anhydrides/chemistry , Animals , Antigens, Neoplasm/immunology , Cell Line , Chemical Precipitation , Dextrans/chemical synthesis , Female , Fluorescence , Fluorescent Dyes/metabolism , Glutarates/chemical synthesis , Glutarates/chemistry , Hydrogen-Ion Concentration , Immunity , Immunization , Interferon-gamma/biosynthesis , Mice , Mice, Inbred C57BL , Ovalbumin/metabolism , Particle Size , Pyrenes/chemistry , Static Electricity , Subcutaneous Tissue/pathology , T-Lymphocytes, Cytotoxic/immunology , TitrimetryABSTRACT
The influence of reaction vessel diameter on the sonochemical yield was investigated by using reaction vessels with five different diameters. It was revealed that the formation of H(2)O(2) and chloride ion, from the sonolysis of pure water and 1,2,4-trichlorobenzene aqueous solution, was affected by the reaction vessel diameter. That is, these yields increased as the reaction vessel diameter increased up to ø 90 mm and then decreased over ø 90 mm. From the analyses of the measurement of sonochemiluminescence and the calorimetry, it was suggested that active cavitation bubbles were formed at certain zones. In the case of a larger diameter reaction vessel, it was suggested that bubble nuclei that have not grown up to the resonance size, escaped from the sonication zone to the non-sonication zone and dissolved away. As a result, the number of active cavitation bubbles and the yields of H(2)O(2) and chloride ion would decrease in the case of a larger diameter reaction vessel.
