Dextran derivative-based pH-sensitive liposomes for cancer immunotherapy

Eiji Yuba, Naoki Tajima, Yuta Yoshizaki, Atsushi Harada, Hiroshi Hayashi, Kenji Kono

Research output: Contribution to journalArticlepeer-review

87 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3091-3101
Number of pages11
JournalBiomaterials
Volume35
Issue number9
DOIs
Publication statusPublished - 2014 Mar
Externally publishedYes

Keywords

  • Cancer immunotherapy
  • Cellular immunity
  • Cytoplasmic delivery
  • Dendritic cell
  • Dextran
  • PH-Sensitive liposome

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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