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Directing Nanoparticle Biodistribution through Evasion and Exploitation of Stab2-Dependent Nanoparticle Uptake

Up to 99% of systemically administered nanoparticles are cleared through the liver. Within the liver, most nanoparticles are thought to be sequestered by macrophages (Kupffer cells), although significant nanoparticle interactions with other hepatic cells have also been observed. To achieve effective cell-specific targeting of drugs through nanoparticle encapsulation, improved mechanistic understanding of nanoparticle–liver interactions is required. Here, we show the caudal vein of the embryonic zebrafish (Danio rerio) can be used as a model for assessing nanoparticle interactions with mammalian liver sinusoidal (or scavenger) endothelial cells (SECs) and macrophages. We observe that anionic nanoparticles are primarily taken up by SECs and identify an essential requirement for the scavenger receptor, stabilin-2 (stab2) in this process. Importantly, nanoparticle–SEC interactions can be blocked by dextran sulfate, a competitive inhibitor of stab2 and other scavenger receptors. Finally, we exploit nanoparticl...

Authors:   Frederick Campbell; Frank L. Bos; Sandro Sieber; Gabriela Arias-Alpizar; Bjørn E. Koch; Jörg Huwyler; Alexander Kros; Jeroen Bussmann
Journal:   ACS Nano
Year:   2018
DOI:   10.1021/acsnano.7b06995
Publication date:   18-Jan-2018
Facts, background information, dossiers
  • cells
  • zebrafish
  • receptors
  • macrophages
  • endothelial cells
  • drugs
  • dextran sulfate
More about American Chemical Society Publications
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