Galactosylated LDL nanoparticles: A novel targeting delivery system to deliver antigen to macrophages and enhance antigen specific T cell responses

Fang Wu, Sherry A. Wuensch, Mitra Azadniv, Mohammad R. Ebrahimkhani, I. Nicholas Crispe

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

We aim to define the role of Kupffer cells in intrahepatic antigen presentation, using the selective delivery of antigen to Kupffer cells rather than other populations of liver antigen-presenting cells. To achieve this we developed a novel antigen delivery system that can target antigens to macrophages, based on a galactosylated low-density lipoprotein nanoscale platform. Antigen was delivered via the galactose particle receptor (GPr), internalized, degraded and presented to T cells. The conjugation of fluoresceinated ovalbumin (FLUO-OVA) and lactobionic acid with LDL resulted in a substantially increased uptake of FLUO-OVA by murine macrophage-like ANA1 cells in preference to NIH3T3 cells, and by primary peritoneal macrophages in preference to primary hepatic stellate cells. Such preferential uptake led to enhanced proliferation of OVA specific T cells, showing that the galactosylated LDL nanoscale platform is a successful antigen carrier, targeting antigen to macrophages but not to all categories of antigen presenting cells. This system will allow targeted delivery of antigen to macrophages in the liver and elsewhere, addressing the question of the role of Kupffer cells in liver immunology. It may also be an effective way of delivering drugs or vaccines directly at macrophages.

Original languageEnglish (US)
Pages (from-to)1506-1517
Number of pages12
JournalMolecular Pharmaceutics
Volume6
Issue number5
DOIs
StatePublished - Oct 5 2009

Keywords

  • Antigen delivery system
  • Fluorescence conjugated ovalbumin
  • Galactose particle receptor
  • LDL
  • Macrophages
  • Nanoscale platform
  • Proliferation of T cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

Fingerprint Dive into the research topics of 'Galactosylated LDL nanoparticles: A novel targeting delivery system to deliver antigen to macrophages and enhance antigen specific T cell responses'. Together they form a unique fingerprint.

  • Cite this