Phenotype Determines Nanoparticle Uptake by Human Macrophages from Liver and Blood.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • MacParland, SA; Tsoi, KM; Ouyang, B; Ma, X-Z; Manuel, J; Fawaz, A; Ostrowski, MA; Alman, BA; Zilman, A; Chan, WCW; McGilvray, ID

Published Date

  • March 2017

Published In

Volume / Issue

  • 11 / 3

Start / End Page

  • 2428 - 2443

PubMed ID

  • 28040885

Pubmed Central ID

  • 28040885

Electronic International Standard Serial Number (EISSN)

  • 1936-086X

International Standard Serial Number (ISSN)

  • 1936-0851

Digital Object Identifier (DOI)

  • 10.1021/acsnano.6b06245

Language

  • eng