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

Campbell, Frederick and Bos, Frank L. and Sieber, Sandro and Arias-Alpizar, Gabriela and Koch, Björn E. and Huwyler, Jörg and Kros, Alexander and Bussmann, Jeroen. (2018) Directing Nanoparticle Biodistribution through Evasion and Exploitation of Stab2-Dependent Nanoparticle Uptake. ACS Nano, 12 (3). pp. 2138-2150.

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Official URL: https://edoc.unibas.ch/62727/

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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.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmaceutical Technology (Huwyler)
UniBasel Contributors:Huwyler, Jörg and Sieber, Sandro
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Chemical Society
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:09 Sep 2020 10:27
Deposited On:09 Sep 2020 10:27

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