期刊
ACS NANO
卷 12, 期 3, 页码 2138-2150出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.7b06995
关键词
endothelial cells; scavenger receptor; nanomedicine; liposomes; stabilin; zebrafish; targeted drug delivery
类别
资金
- Netherlands Organization for Scientific Research (NWO) [12520, 724.014.001]
- Stiftung zur Forderung des pharmazeutischen Nachwuchses in Basel
- Freiwilligen Akademischen Gesellschaft Basel
- Dutch Cancer Society (KWF) [6660]
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 nano particle 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.
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