Biomedical Engineering Reference
In-Depth Information
biodistribution and also for interactions occurring inside cells and finally also for the
outcome of toxicity studies. In addition, we summarized what approaches are avail-
able and useful to study nanomaterials
in situ
with respect to available model fluids
and also with respect to techniques that are appropriate depending on the question
underlying the study.
Studying nanoparticles in serum-containing cell culture medium is a useful and
reasonable approach to understand changes likely to occur under conditions of
in
vitro
testing. In addition, human plasma or serum is easily available to analyze
changes in nanomaterials occurring inside the blood circulation. For the inhalation
route, the picture is a little bit more diverse, as plenty of different protocols exist for
obtaining more or less physiologically relevant lung lining fluids. There is a direct
access to native lung lining fluid, but one needs to purify native surfactant from a
diluted BAL fluid in a laborious protocol. Nevertheless, actually quite physiological
model fluids are finally available for studying pulmonary interactions. However, the
situation is completely different for the GIT where gastric juices are not easily acces-
sible and need to be replaced by artificial simulant fluids.
Taken together, although several studies are available reporting on
in situ
char-
acterization of nanomaterials in different biological environments, very few studies
actually put the complete picture together, meaning only a few studies aim at full
in
situ
characterization (e.g. mapping all interacting biomolecules) instead of typically
focusing each study on a certain aspect. For some biomolecules such as sugars that
currently may be out of technical scope as techniques to do so are not readily avail-
able but for lipids or proteins it may well be achievable. Also, only very few studies
try to systematically assess nanomaterial properties
in situ
and in parallel toxicity
in
vitro
and
in vivo
to correlate the results on various levels (
in vitro
versus
in vivo
toxic-
ity;
in situ
characteristics versus
in vitro
/
in vivo
toxicity). Partially this is of course
due to the fact that getting the complete picture is extremely time and cost intensive
and requires technical skills that are hardly found within a single laboratory but also
partly due to the fact that harmonized approaches are currently lacking. Moreover,
harmonized biological model fluids are missing, which then hinders direct compari-
son of results that have already been published in different studies.
We provided insights into
in situ
characterization as being performed within the
project nanoGEM. NanoGEM is one of the integrated efforts to obtain an as com-
plete as possible picture for 16 different nanomaterials in terms of
in situ
character-
ization and also in terms of uptake into cells, toxicity
in vitro
and
in vivo
as well as
toxicity mechanisms. Within nanoGEM, a first correlation of all these data will be
done, however, a more detailed correlation analysis will certainly be valuable.
Finally it will be very interesting to see how hazard ranking of nanomaterials will
change when in parallel to characteristics as-synthesized, the respective character-
istics
in situ
are used. In addition, the
in situ
characteristics need also to be taken
into consideration when developing “nanoQSAR” models. Last but not least, ulti-
mately the characterization of nanomaterials in the respective test system in terms of
agglomeration and also in terms of biomolecule interaction (“molecular fingerprint”)
would eventually enable prediction of biological interactions and possible toxicity of
a material and thus could be a valuable independent step within a complex testing
st rateg y.
Search WWH ::
Custom Search