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

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...

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Bibliographic Details
Published in:Nanomedicine 2021-06, Vol.34, p.102395, Article 102395
Main Authors: Arias-Alpizar, Gabriela, Koch, Bjørn, Hamelmann, Naomi M., Neustrup, Malene A., Paulusse, Jos M.J., Jiskoot, Wim, Kros, Alexander, Bussmann, Jeroen
Format: Article
Language:English
Subjects:
Animals
Anions
Calcium-Binding Proteins - genetics
Calcium-Binding Proteins - physiology
Endothelium - metabolism
Gene Knockdown Techniques
Lipopolysaccharide
Liver endothelium
Nanoparticles
Stabilin
Zebrafish
Zebrafish - embryology
Zebrafish Proteins - genetics
Zebrafish Proteins - physiology
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Summary: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. Hepatic clearance of anionic nanoparticles represented by a zebrafish model containing scavenging endothelial cells (SECs; functionally equivalent to liver sinusoidal endothelial cells), which allows direct visualization of nanoparticle uptake in this cell type in vivo. We show a requirement for a scavenger receptor Stabilin-1 in the binding and uptake of small nanoparticles (
ISSN:1549-9634
1549-9642
DOI:10.1016/j.nano.2021.102395