TY - JOUR
T1 - Galactosylated LDL nanoparticles
T2 - A novel targeting delivery system to deliver antigen to macrophages and enhance antigen specific T cell responses
AU - Wu, Fang
AU - Wuensch, Sherry A.
AU - Azadniv, Mitra
AU - Ebrahimkhani, Mohammad R.
AU - Crispe, I. Nicholas
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2009/10/5
Y1 - 2009/10/5
N2 - 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.
AB - 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.
KW - Antigen delivery system
KW - Fluorescence conjugated ovalbumin
KW - Galactose particle receptor
KW - LDL
KW - Macrophages
KW - Nanoscale platform
KW - Proliferation of T cells
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U2 - 10.1021/mp900081y
DO - 10.1021/mp900081y
M3 - Article
C2 - 19637876
AN - SCOPUS:70350068879
SN - 1543-8384
VL - 6
SP - 1506
EP - 1517
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
IS - 5
ER -