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Stab2-Mediated Clearance of Supramolecular Polymer Nanoparticles in Zebrafish Embryos
journal contribution
posted on 2020-02-21, 19:10 authored by Victorio Saez Talens, Gabriela Arias-Alpizar, D. M. M. Makurat, Joyal Davis, Jeroen Bussmann, Alexander Kros, Roxanne E. KieltykaSupramolecular
polymers are attractive scaffolds for use as nanocarriers
in drug delivery thanks to their modularity and easy fabrication;
however, a molecular view into their in vivo behavior is lacking.
Herein, we prepare fluorescent squaramide-based supramolecular polymer
nanoparticles that range from fibers to spheres while maintaining
their surface chemistry and near-neutral surface charge by a co-assembly
approach involving a sulfo-cyanine-labeled monomer to track their
in vivo biodistribution behavior and clearance in optically transparent
zebrafish embryos. Evasion of macrophages, localization of the fibrillar
aggregates in the caudal vein, and association with scavenger endothelial
cells are observed. The interaction of the fibrillar supramolecular
nanoparticles with the caudal vein is abrogated in gene-edited zebrafish
lacking Stabilin-2, a receptor analogously found in the mammalian
liver, providing a molecular view into their interaction with scavenger
endothelial cells. We further show that this interaction can be tuned
based on the choice of monomer and its resultant self-assembly.
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supramolecular polymer nanoparticlesscavenger endothelial cellsreceptor analogously foundprepare fluorescent squaramidedrug delivery thanksneutral surface chargefibrillar supramolecular nanoparticlesvivo biodistribution behaviorassembly approach involvingvivo behaviorsurface chemistryfibrillar aggregatestuned basedresultant selfmolecular viewmammalian livereasy fabricationcaudal veinattractive scaffolds
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