title: Galactosylated LDL nanoparticles: a novel targeting delivery system to deliver antigen to macrophages and enhance antigen specific T cell responses.
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.
authors.affiliation: David H. Smith Center for Vaccine Biology and Immunology, The Aab Institute for Biomedical Research, Department of Microbiology, University of Rochester Medical Center, Rochester, New York 14642, USA. fwu5@buffalo.edu
authors.forename: Fang
authors.initials: F
authors.lastname: Wu
authors.forename: Sherry A
authors.initials: SA
authors.lastname: Wuensch
authors.forename: Mitra
authors.initials: M
authors.lastname: Azadniv
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Ebrahimkhani
authors.forename: I Nicholas
authors.initials: IN
authors.lastname: Crispe
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000008:administration & dosage*; D002460:Cell Line; D004187:Disaccharides; D016503:Drug Delivery Systems; D004705:Endocytosis; D005260:Female; D017127:Glycation End Products, Advanced; D055166:Hepatic Stellate Cells / Q000276:immunology / Q000378:metabolism; D066298:In Vitro Techniques; D007728:Kupffer Cells / Q000276:immunology / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000737:chemistry*; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity / Q000648:ultrastructure; D036103:Nanotechnology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011956:Receptors, Cell Surface / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D000093844:Glycated Proteins
chemical_list: D000941:Antigens; D004187:Disaccharides; D017127:Glycation End Products, Advanced; D008077:Lipoproteins, LDL; D010047:Ovalbumin; D011956:Receptors, Cell Surface; C042851:fluorescein-ovalbumin; C039707:galactose receptor; C031797:glycated lipoproteins, LDL; D000093844:Glycated Proteins; C005608:lactobionic acid