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

Authors :
Campbell, Frederick
Bos, Frank L.
Sieber, Sandro
Arias-Alpizar, Gabriela
Koch, Bjørn E.
Huwyler, Jörg
Kros, Alexander
Bussmann, Jeroen
Source :
ACS Nano; January 2018, Vol. 12 Issue: 3 p2138-2150, 13p
Publication Year :
2018

Abstract

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 stab2and other scavenger receptors. Finally, we exploit nanoparticle–SEC interactions to demonstrate targeted intracellular drug delivery resulting in the selective deletion of a single blood vessel in the zebrafish embryo. Together, we propose stab2inhibition or targeting as a general approach for modifying nanoparticle–liver interactions of a wide range of nanomedicines.

Details

Language :
English
ISSN :
19360851 and 1936086X
Volume :
12
Issue :
3
Database :
Supplemental Index
Journal :
ACS Nano
Publication Type :
Periodical
Accession number :
ejs44505445
Full Text :
https://doi.org/10.1021/acsnano.7b06995