pH-Sensitive fusogenic polymer-modified liposomes as a carrier of antigenic proteins for activation of cellular immunity

Biomaterials. 2010 Feb;31(5):943-51. doi: 10.1016/j.biomaterials.2009.10.006. Epub 2009 Oct 21.

Abstract

By modification of liposomes with poly(glycidol) derivatives such as succinylated poly(glycidol) and 3-methylglutarylated poly(glycidol), we have developed functional liposomes that generate fusion ability at mildly acidic pH. We investigated the feasibility of these polymer-modified liposomes as a carrier of antigenic proteins for induction of cellular immunity. These pH-sensitive fusogenic liposomes encapsulating ovalbumin (OVA) were applied to DC2.4 cells, a murine dendritic cell line. Observation with confocal laser scanning microscopy showed that these polymer-modified liposomes were taken up efficiently by the cells, thereafter delivering their contents into the cytosol, probably through fusion with endosomal membranes. Murine bone marrow-derived dendritic cells treated with polymer-modified liposomes encapsulating OVA stimulated CD8-OVA1.3 cells more strongly than OT4H.1D5 cells, indicating that the liposomes induced MHC class I-restricted presentation. Furthermore, administration of the polymer-modified, OVA-loaded liposomes from nasal cavities of mice induced stronger cellular immune responses than the OVA-loaded plain liposomes. Because the ability of the polymer-modified liposomes to activate cellular immunity was comparable to that of Freund's complete adjuvant, which is a widely used adjuvant, they potentially have use in production of efficient vaccines for immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / administration & dosage*
  • Antigens / chemistry
  • Cell Line
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Hydrogen-Ion Concentration
  • Immunity, Innate / drug effects
  • Immunity, Innate / immunology*
  • Liposomes / chemistry*
  • Materials Testing
  • Mice
  • Ovalbumin / administration & dosage*
  • Ovalbumin / chemistry

Substances

  • Antigens
  • Liposomes
  • Ovalbumin