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

• Published in: Small (Weinheim an der Bergstrasse, Germany) Germany), 2020-02, Vol.16 (5), p.e1906719-n/a
• Main Authors: Dal, Nils‐Jørgen Knudsen, Kocere, Agnese, Wohlmann, Jens, Van Herck, Simon, Bauer, Tobias A., Resseguier, Julien, Bagherifam, Shahla, Hyldmo, Hilde, Barz, Matthias, De Geest, Bruno G., Fenaroli, Federico
• Format: Article
• Language: English
• Subjects: Animals; Blood circulation; circulation time; Embryo, Nonmammalian; Embryos; Endothelial cells; Endothelial Cells - metabolism; Macrophages; Macrophages - metabolism; Mathematical models; Mice; Nanoparticles; Nanoparticles - metabolism; Nanotechnology; Parameters; Quantitative analysis; Rodents; Vertebrates; Zebrafish
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.201906719

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. Upon intravenous injection of fluorescent nanoparticles, the transparency of zebrafish embryos allows rapid analysis of the decrease of fluorescence over time in the blood vessels. Quantification of nanoparticle circulation times reveals the ability of zebrafish to predict the results in the mouse model. Moreover, availability of transgenic lines enables careful evaluation of the interaction of nanoparticles with macrophages and endothelial cells.