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

Abstract

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.

Nanoparticles in the Biological Context: Surface Morphology and Protein Corona Formation

“…[ 80 ] Here, polymer micelles with a hydrophilic polysarcosine shell show a low unspecific uptake and a long circulation time. [ 81 ]…”

“…[80] Here, polymer micelles with a hydrophilic polysarcosine shell show a low unspecific uptake and a long circulation time. [81] Now, given that it has some advantages to prepare nanoparticles with a neglectable protein corona, what are reasonable methods to make them? At first, the proteins should be kept away from the sharp interface and here steric repulsion seems most reasonable.…”

Real-time imaging of polymersome nanoparticles in zebrafish embryos engrafted with melanoma cancer cells: Localization, toxicity and treatment analysis

“…It is also an attractive system to follow the fate of injected NP relative to the tumour. We recently showed how the zebrafish can help in predicting the biodistribution of intravenously injected NP in mice [47] . The far red-labelled PEG-PDPA NP that we tested in our zebrafish cancer system accumulated in the tumour mass in a significant manner compared to neighbouring tissues; however they did so much less (about 2%) than in our zebrafish tuberculosis model system in which up to 20% of the injected NP could be found in the proximity of the Mycobacterium marinum granulomas [21] .…”

Nanotechnology‐Based Targeted Drug Delivery: An Emerging Tool to Overcome Tuberculosis

“…[ 67 ] Furthermore, the pharmacokinetics of liposomes and nanoparticles (circulation time, interactions with key target cells, macrophages, and endothelial cells) are similar in zebra fish and mice models according to a recent study carried out by Dal et al. [ 75 ]…”