Directing Nanoparticle Biodistribution through Evasion and Exploitation of Stab2-Dependent Nanoparticle Uptake
| Autor: | Sandro Sieber, Alexander Kros, Gabriela Arias-Alpizar, Frank L. Bos, Jörg Huwyler, Jeroen Bussmann, Frederick Campbell, Bjørn E. V. Koch |
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| Rok vydání: | 2018 |
| Předmět: |
liposomes
0301 basic medicine Biodistribution Embryo Nonmammalian General Physics and Astronomy Nanoparticle 02 engineering and technology Physics and Astronomy(all) Article targeted drug delivery scavenger receptor Mice 03 medical and health sciences Materials Science(all) stabilin Animals Tissue Distribution General Materials Science Scavenger receptor Zebrafish Engineering(all) Receptors Scavenger Liposome biology Chemistry Macrophages Calcium-Binding Proteins General Engineering Zebrafish Proteins zebrafish 021001 nanoscience & nanotechnology biology.organism_classification nanomedicine endothelial cells 030104 developmental biology Targeted drug delivery Hepatocytes Hepatic stellate cell Biophysics Nanoparticles Nanomedicine 0210 nano-technology |
| Zdroj: | ACS Nano ACS Nano, 12(3), 2138. American Chemical Society ACS Nano, 12(3), 2138-2150 |
| ISSN: | 1936-086X 1936-0851 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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