1 research outputs found
Phenotype Determines Nanoparticle Uptake by Human Macrophages from Liver and Blood
A significant challenge to delivering
therapeutic doses of nanoparticles to targeted disease sites is the
fact that most nanoparticles become trapped in the liver. Liver-resident
macrophages, or Kupffer cells, are key cells in the hepatic sequestration
of nanoparticles. However, the precise role that the macrophage phenotype
plays in nanoparticle uptake is unknown. Here, we show that the human
macrophage phenotype modulates hard nanoparticle uptake. Using gold
nanoparticles, we examined uptake by human monocyte-derived macrophages
that had been driven to a “regulatory” M2 phenotype
or an “inflammatory” M1 phenotype and found that M2-type
macrophages preferentially take up nanoparticles, with a clear hierarchy
among the subtypes (M2c > M2 > M2a > M2b > M1). We also
found that stimuli such as LPS/IFN-γ rather than with more “regulatory”
stimuli such as TGF-β/IL-10 reduce per cell macrophage nanoparticle
uptake by an average of 40%. Primary human Kupffer cells were found
to display heterogeneous expression of M1 and M2 markers, and Kupffer
cells expressing higher levels of M2 markers (CD163) take up significantly
more nanoparticles than Kupffer cells expressing lower levels of surface
CD163. Our results demonstrate that hepatic inflammatory microenvironments
should be considered when studying liver sequestration of nanoparticles,
and that modifying the hepatic microenvironment might offer a tool
for enhancing or decreasing this sequestration. Our findings also
suggest that models examining the nanoparticle/macrophage interaction
should include studies with primary tissue macrophages