Intestinal, Liver and Vascular Nanoparticle Toxicity:

Development and evaluation of a novel tool for physiologically

accurate data generation

A European Integrated Project supported through the Seventh Framework Programme

for Research and Technological Development
 Improving our ability to understand and assess the safety
and toxicity of novel materials, particularly nanoparticles.

There is currently a high level of concern
about the potential risks to health posed by
novel substances, particularly nanoparticles.
Governments and regulatory bodies are asked
to set guidelines or controls that will help
protect those involved in the manufacture or
use of these materials. However, there are
serious gaps in our understanding of the way
such materials interact with the human body
or the level of risk that exposure to them might
involve. This project aims to address these
needs through improving our understanding
and providing tools and assays that might form
the basis of new testing methods for safety
and toxicity without the use of animals.

Summary
The InLiveTox project will develop an improved in vitro model for the study of nanoparticle (NP)
uptake, transport and cellular interaction, thus advancing our understanding of NP toxicity.
Biological tissue models will be implemented in a microfabricated compartmental cell culture
system that allows multiple cell types to be addressed and investigated in combination.

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 being addressed by this project are:

• How do these tissues individually respond to NPs?
• How do the interactions between the different tissues modulate their responses?
• How does inflammation affect the toxicity of NPs and their ability to cross the intestinal
barrier?
• Which physico-chemical characteristics of NPs influence their uptake by intestinal epithelial
cells and their subsequent interactions with endothelial and liver cells?

Objectives
The objective of InLiveTox is 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 models of target tissues such as the GI tract, the liver and the endothelium will
be interconnected via a microfluidics system so that knock-on and cross talk effects between
organs and tissues can be monitored.
The in vitro system will be validated by an in vivo study of NP toxicity by ingestion
in rats carried out in parallel.
InLiveTo system

3D co-culture: intestinal epithelial cell,

dendritic cell and macrophage

Endothelial cells

Liver cells

Nanoparticles

Methodology & workflow

WP1: Development of the microfluidic systems

WP2: Set up in vitro biological models for

assessing NP toxicity
WP3: Implement biological models in the
microfluidic system & development
WP4: In vivo assays
WP5: Validation of the system
and analysis of NP toxicity by
ingestion

WP6: Dissemination, Exploitation and Knowledge Transfer

WP7: Project Management
Year 1 Year 2 Year 3

Perspectives
The system being developed in the InLiveTox project will
be much easier to use, 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. In this project, the focus will be on NP toxicology,
but a similar system could also be widely used for various
applications in toxicology and pharmacology.
Consortium
The three year project will be carried out by an interdisciplinary consortium
including European leaders in nanotoxicology (Edinburgh Napier University,
Universität des Saarlandes, HelmholtzZentrum münchen), and engineering
(Centre Suisse d’Electronique et de Microtechnique, Università di Pisa) together
with a key American nanotoxicology group (University of Rochester). In addition, the project benefits from
input from an Industrial and Authorities Advisory Group whose members come from the pharmaceutical,
cosmetics, food and household products industries and European regulatory bodies.

Nanosafety cluster
InLiveTox is a member of the European Nanosafety cluster together with ENPRA, ENNSATOX,
HINAMOX and NEPHH FP7 projects.

Acknowledgments
The InLiveTox project is supported by the European Commission through the Seventh Framework
Programme for Research and Technological Development. This 3 year project will run from 1st May 2009
to 30th April 2012.

www.inlivetox.eu

Contacts Dissemination & Exploitation Manager

Dr J. Malcolm WILKINSON - KIRKSTALL Ltd
Scientific coordination United Kingdom - jmw@kirkstall.org
Dr Martha LILEY - CSEM SA
Centre Suisse d’Electronique et de Microtechnique Project Manager
Switzerland - mliley@csem.ch ALMA Consulting Group SAS - France