PUBLICATION
Directing Nanoparticle Biodistribution Through Evasion and Exploitation of Stab2-Dependent Nanoparticle Uptake
- Authors
- Campbell, F., Bos, F.L., Sieber, S., Arias-Alpizar, G., Koch, B.E., Huwyler, J., Kros, A., Bussmann, J.
- ID
- ZDB-PUB-180111-10
- Date
- 2018
- Source
- ACS nano 12(3): 2138-2150 (Journal)
- Registered Authors
- Bos, Frank, Bussmann, Jeroen, Koch, Bjorn
- Keywords
- none
- MeSH Terms
-
- Animals
- Embryo, Nonmammalian/metabolism
- Embryo, Nonmammalian/ultrastructure
- Endothelial Cells/metabolism*
- Hepatocytes/metabolism*
- Liposomes/analysis
- Liposomes/metabolism
- Macrophages/metabolism*
- Mice
- Nanoparticles/analysis
- Nanoparticles/metabolism*
- Receptors, Scavenger/metabolism*
- Tissue Distribution
- Zebrafish/embryology*
- Zebrafish/metabolism
- PubMed
- 29320626 Full text @ ACS Nano
Citation
Campbell, F., Bos, F.L., Sieber, S., Arias-Alpizar, G., Koch, B.E., Huwyler, J., Kros, A., Bussmann, J. (2018) Directing Nanoparticle Biodistribution Through Evasion and Exploitation of Stab2-Dependent Nanoparticle Uptake. ACS nano. 12(3):2138-2150.
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 stab2 and 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 stab2-inhibition or -targeting as a general approach for modifying nanoparticle-liver interactions of a wide range of nanomedicines.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping