http://www.alphagalileo.org/ViewItem.aspx?ItemId=172205&CultureCode=en
03 February 2017
Université de Genève
The use of nanoparticles —
small, virus-sized elements developed under laboratory conditions — is
increasingly widespread in the world of biomedicine. This
rapidly-evolving technology offers hope for many medical applications,
whether for diagnosis or therapies. In oncology, for example, the
growing body of research suggests that, thanks to nanoparticles,
treatment will soon become more precise, more effective and less painful
for the patients. However, the way nanoparticles interact with the
immune system remained unclear and unpredictable until recently,
restricting their potential medical use. Today, researchers from the
universities of Geneva (UNIGE) and Fribourg (UNIFR), Switzerland, are
close to solving the problem: they have devised a rapid screening method
to select the most promising nanoparticles, thereby fast-tracking the
development of future treatments. In less than a week, they are able to
determine whether nanoparticles are compatible or not with the human
body — an analysis that previously required several months of work. This
discovery, which is described in the journal Nanoscale, may well lead to the swift, safe and less expensive development of nanotechnology applied to medicine.
Nanoparticles measure between 1 and 100
nanometres, approximately the size of a virus. Their very minuteness
means that they have the potential to be used in a wide range of medical
applications: serving as markers for diagnosis, for example, or
delivering therapeutic molecules to the exact spot in the body where the
drug is intended to act. However, before being applied to the medical
field, nanoparticles must prove (i) that they are safe for the human
body and (ii) that they are capable of bypassing the immune system so
they can have an effect. “Researchers can spend years developing a
nanoparticle, without knowing what impact it will have on a living
organism,” explains Carole Bourquin, professor in the medicine and
science faculties at UNIGE and project leader. “So there was a real need
to design an effective screening method that could be implemented at
the beginning of the development process. Indeed, if the nanoparticles
aren’t compatible, several years of research were simply thrown away.»
Macrophages orchestrate the immune response
When a foreign element — any foreign
element — enters the body, the immune system is activated. Macrophages
are always found on the front line, large cells that «ingest» invaders
and trigger the immune response. Nanoparticles are no exception to this
rule. The way macrophages react to the nanoparticle under investigation
then predicts the biocompatibility of the product. «When you begin to
develop a new particle, it’s very difficult to ensure that the recipe is
exactly the same every time,» points out Inès Mottas, the first author.
«If we test different batches, the results may differ. Hence our idea
of finding a way to test the three parameters simultaneously — and on
the same sample — to establish the product’s biocompatibility: its
toxicity, its ability to activate the immune system, and the capacity of
the macrophages to ingest them.»
The ideal medical nanoparticle should
therefore not be toxic (it should not kill the cells); should not be
entirely ingested by the macrophages (so that it retains its power to
act); and should limit the activation of the immune system (to avoid
adverse side-effects).
Evaluating the three key elements simultaneously
Until now, evaluating the
biocompatibility of nanomaterials was a laborious task that took several
months and posed reproducibility problems, since not all the tests were
performed on the same batch of particles. Professor Bourquin and her
team used flow cytometry to reach a diagnosis on the three essential
elements in a safe and standardised manner, and in record time. «The
macrophages are brought into contact with the nanoparticles for 24
hours, and are then passed in front of the laser beams. The fluorescence
emitted by the macrophages makes it possible to count them and
characterise their activation levels. Since the particles themselves are
fluorescent, we can also measure the amount ingested by the
macrophages. Our process means we can test the three elements
simultaneously, and we only need a very small amount of particles,»
continues Mottas. «We can obtain a comprehensive diagnosis of the
nanoparticle submitted to us in two or three days.»
The method devised in Geneva and
Freiburg is part of the work carried out within the National Centres of
Competence in Research (NCCR) “Bio-Inspired Materials”, and is already a
great success with scientists striving to develop new particles. It
focuses their work by enabling them to select the most promising
particles quickly. As well as having a financial impact on the cost of
research, this new approach also limits the use of animal testing.
Furthermore, it is opening the door to the increasingly personalized
treatment of certain pathologies. For example, by testing the
nanoparticles on tumour cells isolated from a particular patient, it
should theoretically be possible to identify the most effective
treatment. Only time will tell whether this hypothesis is backed up in
practice.
Attached files
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macrophages with, in green, nanoparticles. ©Laboratoire Bourquin – UNIFR/UNIGE
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