TY - JOUR
T1 - Stabilin-1 is required for the endothelial clearance of small anionic nanoparticles
AU - Arias-Alpizar, S.G.
AU - Koch, B.
AU - Hamelmann, Naomi Marie
AU - Neustrup, M.A.
AU - Paulusse, J.M.J.
AU - Jiskoot, W.
AU - Kros, A.
AU - Bussmann, J.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - 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.
AB - 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.
U2 - 10.1016/j.nano.2021.102395
DO - 10.1016/j.nano.2021.102395
M3 - Article
VL - 34
JO - Nanomedicine : nanotechnology, biology and medicine
JF - Nanomedicine : nanotechnology, biology and medicine
SN - 1549-9634
M1 - 102395
ER -