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.

Automated summary

Metallic nanoparticles and ions have different impacts on human cell responses, with their chemical properties being more important than known biological functions. The response to nanoparticles is mainly influenced by the ions they contain and depends on their solubility. Nanoparticles affect cell response by altering genes related to intracellular transport and the cytoskeleton. Moreover, several metals trigger a cell response governed by metallothioneins, along with specific signatures for each element.