Stab2-Mediated Clearance of Supramolecular Polymer Nanoparticles in Zebrafish Embryos.

Victorio Saez Talens,Joyal Davis,Gabriela Arias-Alpizar,Alexander Kros,D M M Makurat,Roxanne E Kieltyka,Jeroen Bussmann

doi:10.1021/acs.biomac.9b01318

Victorio Saez Talens, Joyal Davis + Show 5 more

Open Access

https://doi.org/10.1021/acs.biomac.9b01318

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Journal: Biomacromolecules	Publication Date: Feb 21, 2020
Citations: 8	License type: CC BY 4.0

Affiliation: Leiden University

Abstract

Supramolecular 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.

Highlights

Significant effort has been dedicated to the design and synthesis of nanoparticle carriers (
Nanoparticles of varied features, including size, shape, surface charge, functionality, and elasticity, have been prepared.[1−4] Irrespective of their designs, it has been demonstrated that >99% of such nanoparticles are cleared by the liver, yet the complete structure−activity relationships that underlie these processes remain unclear due to the inherent difficulty to visualize these cellular mechanisms in mammalian models.[2,5]
We have demonstrated the functional homology of the zebrafish embryonic caudal vein (CV) to the mammalian liver at the molecular level, enabling the rapid screening of nanoparticle biodistribution and tissue targeting in vivo.[5]