The InLiveTox project will form an interdisciplinary consortium at the European level, together with a key American research group to develop an improved in vitro model for the study of nanoparticle (NP) uptake, transport and cellular interaction, thus advancing our understanding of NP toxicity. Rather than repeat what has, or is being done in the field of aerosol NP and lung toxicology, InLiveTox will focus on the impact of NP exposure via ingestion, in the healthy and diseased gastrointestinal (GI) tract, vascular endothelium and liver.
The key questions in this study are:
(i) How do these tissues individually respond to NPs?
(ii) How do the interactions between the different tissues modulate their responses?
(iii) How does inflammation affect the toxicity of NPs and their ability cross the intestinal barrier?
(iv) Which physico-chemical characteristics of NPs influence their uptake by intestinal epithelial cells and their subsequent interactions with endothelial and liver cells?
The objective of InLiveTox will be to develop a novel modular microfluidics-based in vitro test system modelling the response of cells and tissues to the ingestion of NPs. Cell culture modules of target tissues such as the GI tract, the liver and the endothelium will be connected via a microfluidics system so that knock-on and cross talk effects between organs and tissues can be monitored.
A major innovative aspect of the InLiveTox project pertains to the implementation of biological tissue models in a microfabricated compartmental cell culture system that allows multiple cell types to be addressed and investigated in combination. This system will be much easier, more convenient and ethically less questionable than animal testing, as well as more relevant than the in vitro single cell /co-culture models currently used. For this study, applications of the model will focus on NP toxicology, but the system could also be widely used in various applications of toxicology and pharmacology.