Importance of Metal Biotransformation in Cell Response to Metallic Nanoparticles: A Transcriptomic Meta-analysis Study

Metallic nanoparticles are increasingly present in our
environment,
raising concerns on their interactions with living organisms and potential
toxicity. Indeed, metallic nanoparticles release metal ions that can
be toxic, bioessential, therapeutically active, or combine several
of these features. However, human cell responses to different metallic
nanoparticles and ions have rarely been compared so far. We propose
here a meta-analysis of the transcriptomic responses of human cells
to nanoparticles and ions of various metals (titanium, iron, copper,
zinc, silver, cadmium, platinum, gold), in order to identify the commonalities
and differences between cell responses to these compounds. This analysis
revealed that the chemical properties of metals are more important
than their known biological functions (i.e., essential metals, toxicity)
in governing the cell transcriptome. Particularly, we evidence that
the response to nanoparticles is dominated by the response to the
ions they contain, and depend on the nanoparticles’ solubility.
The formulation as nanoparticles impacts the cell response at lower
intensity than the released ions, by altering genes related to vesicle
intracellular transport and the cytoskeleton. Moreover, we put into
light that several metals (i.e., copper, zinc, silver, cadmium, and
gold) trigger a common cell response governed by metallothioneins,
which coexist with singular signatures that are specific to a given
element.