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RESEARCH PRODUCT

Zebrafish Embryos Allow Prediction of Nanoparticle Circulation Times in Mice and Facilitate Quantification of Nanoparticle–Cell Interactions

Hilde HyldmoJulien RességuierNils-jørgen Knudsen DalAgnese KocereSimon Van HerckBruno G. De GeestMatthias BarzJens WohlmannTobias BauerShahla BagherifamFederico Fenaroli

subject

NANOCARRIERSEmbryo Nonmammalianmiceanimal structurescirculation timeCellNanoparticleLIPOSOMES02 engineering and technology010402 general chemistry01 natural sciencesSEQUENCEBiomaterialsMiceDELIVERYmedicineMedicine and Health SciencesAnimalsGeneral Materials ScienceZebrafishZebrafishbiologyChemistryMacrophagesEndothelial CellsOptical transparencyPLGAGeneral ChemistryTARGETING MACROPHAGES021001 nanoscience & nanotechnologybiology.organism_classificationzebrafishCANCER0104 chemical sciencesCell biologymacrophagesChemistrymedicine.anatomical_structureCell cultureembryonic structuresZebrafish embryoNanoparticlesCirculation timenanoparticlesNanocarriers0210 nano-technologyANTIBIOTICSBiotechnology

description

The zebrafish embryo is a vertebrate well suited for visualizing nanoparticles at high resolution in live animals. Its optical transparency and genetic versatility allow noninvasive, real-time observations of vascular flow of nanoparticles and their interactions with cells throughout the body. As a consequence, this system enables the acquisition of quantitative data that are difficult to obtain in rodents. Until now, a few studies using the zebrafish model have only described semiquantitative results on key nanoparticle parameters. Here, a MACRO dedicated to automated quantitative methods is described for analyzing important parameters of nanoparticle behavior, such as circulation time and interactions with key target cells, macrophages, and endothelial cells. Direct comparison of four nanoparticle (NP) formulations in zebrafish embryos and mice reveals that data obtained in zebrafish can be used to predict NPs' behavior in the mouse model. NPs having long or short blood circulation in rodents behave similarly in the zebrafish embryo, with low circulation times being a consequence of NP uptake into macrophages or endothelial cells. It is proposed that the zebrafish embryo has the potential to become an important intermediate screening system for nanoparticle research to bridge the gap between cell culture studies and preclinical rodent models such as the mouse.

10.1002/smll.201906719http://hdl.handle.net/10852/83840