PUBLICATION

Stabilin-1 is required for the endothelial clearance of small anionic nanoparticles

Authors
Arias-Alpizar, G., Koch, B., Hamelmann, N.M., Neustrup, M.A., Paulusse, J.M.J., Jiskoot, W., Kros, A., Bussmann, J.
ID
ZDB-PUB-210411-8
Date
2021
Source
Nanomedicine : nanotechnology, biology, and medicine   34: 102395 (Journal)
Registered Authors
Bussmann, Jeroen, Koch, Bjorn
Keywords
lipopolysaccharide, liver endothelium, nanoparticles, stabilin, zebrafish
MeSH Terms
  • Animals
  • Anions
  • Calcium-Binding Proteins/genetics
  • Calcium-Binding Proteins/physiology*
  • Endothelium/metabolism*
  • Gene Knockdown Techniques
  • Nanoparticles*
  • Zebrafish/embryology
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
PubMed
33838334 Full text @ Nanomedicine
Abstract
Clearance of nanoparticles (NPs) after intravenous injection - mainly by the liver - is a critical barrier for the clinical translation of nanomaterials. Physicochemical properties of NPs are known to influence their distribution through cell-specific interactions; however, the molecular mechanisms responsible for liver cellular NP uptake are poorly understood. Liver sinusoidal endothelial cells and Kupffer cells are critical participants in this clearance process. Here we use a zebrafish model for liver-NP interaction to identify the endothelial scavenger receptor Stabilin-1 as a non-redundant receptor for the clearance of small anionic NPs. Furthermore, we show that physiologically, Stabilin-1 is required for the removal of bacterial lipopolysaccharide (LPS/endotoxin) from circulation and that Stabilin-1 cooperates with its homolog Stabilin-2 in the clearance of larger (~100 nm) anionic NPs. Our findings allow optimization of anionic nanomedicine biodistribution and targeting therapies that use Stabilin-1 and -2 for liver endothelium-specific delivery.
Genes / Markers
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping