Increasing the versatility of an ex vivo model in nanosafety studies and fibrosis

Nanomaterials are materials in the size range of 1-100 nm, although their classifcation remains still debated in the field. Despite their small size, nanotechnology applications are many and their number is continuously growing in the industry sector as well as in the biomedical field. Nanomedicine field combines chemical and mechanical properties of nanomaterials to prepare e.g. new drugs that may reach the intended target with higher efficiency than standard drugs. However, nanomaterials are everywhere and humans can be exposed to them via external (air, water, food, etc.) and/or internal sources, therefore exposed to them also unintentionally. For this reason it is pivotal to investigate their potential toxicity in cells and organism. Nanosafety, it is the discipline that studies the potential hazards of nanomaterials and their interference with biological systems. One of the major problem in this field, it is to find reliable advanced in vitro models. In this thesis, Precision-Cut Tissue Slices, 3D model, derived from mice, rat and importantly human are explored as alternative to in vivo and in vitro models to study nanoparticles behavior and potential toxicity ex vivo using real pieces of liver, lung and kidney. Tissue slices have the great advantage to maintain intact the cell ratio and architecture of the organ from where they are extracted. Briefly, we demonstrate that it is possible to reproduce ex vivo key features of in vivo biodistribution, e.g. nanoparticles are preferentially accumulated in macrophages. Furthermore, this ex vivo model has been used in the second part of the thesis to study the expression of Vanin 1 protein, in fibrosis.