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: Eiji Yuba, Naoki Tajima, Yuta Yoshizaki, Atsushi Harada, Hiroshi Hayashi, Kenji Kono
• Journal: Biomaterials (Biomaterials) Vol. 35 Issue 9 Pg. 3091-101 (Mar 2014) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 24406217 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Anhydrides
• Antigens, Neoplasm
• Dextrans
• Fluorescent Dyes
• Glutarates
• Liposomes
• Pyrenes
• glutaric anhydride
• Interferon-gamma
• Ovalbumin
• pyrene

Topics

• Anhydrides (chemical synthesis, chemistry)
• Animals
• Antigens, Neoplasm (immunology)
• Cell Line
• Chemical Precipitation
• Dextrans (chemical synthesis, chemistry)
• Female
• Fluorescence
• Fluorescent Dyes (metabolism)
• Glutarates (chemical synthesis, chemistry)
• Hydrogen-Ion Concentration
• Immunity
• Immunization
• Immunotherapy
• Interferon-gamma (biosynthesis)
• Liposomes (chemistry)
• Mice
• Mice, Inbred C57BL
• Neoplasms (immunology, therapy)
• Ovalbumin (metabolism)
• Particle Size
• Pyrenes (chemistry)
• Static Electricity
• Subcutaneous Tissue (pathology)
• T-Lymphocytes, Cytotoxic (immunology)
• Titrimetry