Zebrafish Models for the Safety and Therapeutic Testing of Nanoparticles with a Focus on Macrophages

Abstract

New nanoparticles and biomaterials are increasingly being used in biomedical research for drug delivery, diagnostic applications, or vaccines, and they are also present in numerous commercial products, in the environment and workplaces. Thus, the evaluation of the safety and possible therapeutic application of these nanomaterials has become of foremost importance for the proper progress of nanotechnology. Due to economical and ethical issues, in vitro and in vivo methods are encouraged for the testing of new compounds and/or nanoparticles, however in vivo models are still needed. In this scenario, zebrafish (Danio rerio) has demonstrated potential for toxicological and pharmacological screenings. Zebrafish presents an innate immune system, from early developmental stages, with conserved macrophage phenotypes and functions with respect to humans. This fact, combined with the transparency of zebrafish, the availability of models with fluorescently labelled macrophages, as well as a broad variety of disease models offers great possibilities for the testing of new nanoparticles. Thus, with a particular focus on macrophage–nanoparticle interaction in vivo, here, we review the studies using zebrafish for toxicological and biodistribution testing of nanoparticles, and also the possibilities for their preclinical evaluation in various diseases, including cancer and autoimmune, neuroinflammatory, and infectious diseases.

Zebrafish as a Model System to Study the Mechanism of Cutaneous Wound Healing and Drug Discovery: Advantages and Challenges

“…Clerodendrum cyrthophyllum Turcz (C. Turcz) is a plant that has been used in folk medicine for treating a variety of inflammatory medical conditions such as migraine and rheumatoid arthritis [63]. Prior study of C. Turcz in zebrafish has proven its anti-inflammatory activities, which could affect the cutaneous-wound-healing process.…”

In Vitro and In Vivo Models to Assess the Immune-Related Effects of Nanomaterials

“…Among non-mammalian vertebrates, several fish models are available, including the well-known zebrafish (Danio rerio), which displays both innate and adaptive immunity [62]. Zebrafish larvae are particularly useful for the study of innate immunity in vivo in vertebrates [63] and for assessing the immune effects of nano and micromaterials [64][65][66].…”

Dissolution and Biological Assessment of Cancer-Targeting Nano-ZIF-8 in Zebrafish Embryos

“…21 The transparent protective membrane encircles the embryo, known as a chorion, thereby allowing nanotherapeutics to permeate and be readily visualized. 22,23 Depending on the disease model, various biological aspects including toxicity, 24 hatching, 25 organ development, and behavior 26 can be assessed, all of which support the safety and efficacy assessment of newly developed drug delivery systems. 27−29 Considering this, our interest herein was to ascertain the ability of a cancer-targeting nanotherapeutic system, gemcitabine encapsulated within RGD-functionalized nZIF-8 (GEM⊂RGD@nZIF-8), to promote permeability through the biological barrier and to assess possible toxicity within healthy zebrafish embryos.…”

“…Many important findings in zebrafish development apply to human development due to high genomic similarities (70%). , Owing to their smaller size, zebrafish have high reproducibility and rapid embryo development with optical transparency . The transparent protective membrane encircles the embryo, known as a chorion, thereby allowing nanotherapeutics to permeate and be readily visualized. , Depending on the disease model, various biological aspects including toxicity, hatching, organ development, and behavior can be assessed, all of which support the safety and efficacy assessment of newly developed drug delivery systems. − …”