Timing, hosts and locations of (grouped) events of NanoImpactNet

communication with a variety of groups in EU and US, and Japan
with similar objectives. Key collaborations already exist between
the program and US partners. However, key collaborations also
exist with other major US and Japanese centres, and these have
been aligned to the program (see Section 2.1). Still, we recognise
the need to adopt a more flexible approach that takes account
of realities on the ground after review of these programs,
aligning with those programs that are funded, and newly
emerging ones both in modelling, and in collection of
experimental data.
We consider that these models, and this methodology, will point
the way to the key science, and its relevance for society. A
reductionist approach based on interactions and mechanisms,
gives the capacity to identify and evolve the key characteristics
(size, bare zeta potential, corona composition) of nanoparticles
leading to different impacts, and above all, clearly identify the
causal link between them. This link is the key to safety by
design.
The interaction of the workpackages and the flow of
information between them and the external experimental
projects is shown in the Pert Chart in Figure 4, below.
Figure 4. NanoTransKinetics Pert chart.
5 NanoTransKinetics activities
NanoTransKinetics addresses the following objectives:
• To establish techniques for modeling relationships
between nanoparticle properties and toxicity (including
interactions of nanoparticles with biological systems);
NanoTransKinetics focuses on understanding the mechanisms
of nanoparticle uptake into, and sub-cellular transport within
cells and through biological barriers with the objective of
enabling much more rapid progress towards a screening
approach, where predictions of nanoparticle bioaccumulation
could be made on the basis of limited in vitro screening data.
NanoSafetyCluster - Compendium 2012
NanoTransKinetics is the first integrated effort to develop
phenomenological models based on high quality experimental
data of nanoparticles interactions with cells and biological
barriers. It aims to characterize the hazard posed by
nanoparticles in relation to their ability to cross biological
barriers, based on nanoparticle concentration fluxes (rather
than the traditional ADME approaches which are based on
equilibrium properties, which are not applicable to
nanoparticles as they interact with cells in a biological manner,
and are actively transported within cells. A four tiered approach
(interaction with biological fluids, interaction with cellular
membranes, interaction with cells in vitro, and interaction with
biological barriers, such as the Blood-brain barrier based on in
vitro and in vivo data), as shown graphically in the Pert Chart in
Figure 4, will ensure sufficient understanding of the role of
nanoparticle-protein interactions in mediating nanoparticlemembrane
and nanoparticle-protein-cell interactions, whilst
allowing sufficient flexibility to be built into the models to allow
modeling of data from a wide range of sources, including high
throughput data such as High content analysis, thereby also
providing a useful route for these data to be integrated into
predictive approaches.
• identification of physicochemical properties chosen
for establishing groups of structurally similar particles, the
characterisation and classification techniques, the test methods,
and the relation of structural descriptors to toxicological
targets;
One hypothesis of our approach is that nanoparticles in contact
with biological systems are immediately coated by a layer of
biomolecules which confers to them a “biological identity”
which determines how the particles are seen by the cell, and
how they interact with the cell. However, a deeper view of this
that we have sought to clarify here is that the nanoparticleenvironmental
interaction cannot be ignored. Partner 2 and
Partner 1 were both engaged in a previous EU program (lead by
Partner 2) on gene transfer using liposomal and other carriers
that though overall successful was striking in illustrating how
weak the connection and efficiency between cell level and in
vivo predictions was. Considerable investigation revealed that a
major element of that was that cell culture takes poor account
of the nanoparticle interactions with proteins, extracellular
matrix and other biological environmental aspects. Here these
elements are built into the program. Learning to predict the
biological identities of nanoparticles and to correlate this with
uptake, transport and clearance is the only way that we can
truly determine a priori, the fate and behaviour of nanoparticles,
and their safety implications for human health and the
environment. Thus, the key to establishing categories of
particles is via their biological identity, or what they actually
present to cells. The endpoints that we have chosen to focus on
in this programme are thus interactions with biofluids (e.g.
plasma / cell culture medium), interactions with biological
membranes (involved in uptake processes), interaction with
cells (specifically transport kinetics and sub-cellular
concentrations) and interaction with biological barriers (to
begin the connection to in vivo predictions). Connecting the
biological identity of nanoparticles to specific accumulation in
certain organelles, and consequently to specific impacts such as
apoptosis, enables us to categorize nanoparticles and to begin
the process of predicting biological impacts based on biological
Compendium of Projects in the European NanoSafety Cluster 201