Advantages and Potential Benefits of Using Organoids in Nanotoxicology

Abstract

Organoids are microtissues that recapitulate the complex structural organization and functions of tissues and organs. Nanoparticles have several specific properties that must be considered when replacing animal models with in vitro studies, such as the formation of a protein corona, accumulation, ability to overcome tissue barriers, and different severities of toxic effects in different cell types. An increase in the number of articles on toxicology research using organoid models is related to an increase in publications on organoids in general but is not related to toxicology-based publications. We demonstrate how the quantitative assessment of toxic changes in the structure of organoids and the state of their cell collections provide more valuable results for toxicological research and provide examples of research methods. The impact of the tested materials on organoids and their differences are also discussed. In conclusion, we highlight the main challenges, the solution of which will allow researchers to approach the replacement of in vivo research with in vitro research: biobanking and standardization of the structural characterization of organoids, and the development of effective screening imaging techniques for 3D organoid cell organization.

Keywords: 3D cell cultures; in vitro models; nanomaterials; nanotoxicology; organoids.

Figure 1

Main routes of NP entry into organisms. Most NPs can enter the body through natural barriers, such as the skin, mucous membranes, or vessel walls. At the same time, to study the biodistribution of NPs, it is important to understand how nanoparticles pass through these barriers. For example, NPs that enter the body through the skin can enter vessels by passing through the basolateral membrane and then through the endothelial layer. If the NPs initially enter the vessel, they can leave it via the luminal pathway, first passing the endothelial layer and then the basolateral membrane in the opposite direction.

Figure 2

The combination of high-throughput and high-content studies for organoids requires the development and improvement of several methods, namely the automation of organoid production, the standardization of production methods, and the development of standards for assessing morphological changes in organoids.