Gold and titania nanoparticles accumulated in the body induce late toxic effects and alterations in transcriptional and miRNA landscape

Abstract

The growing production of nanomaterials and their presence in consumer products raises fear about their impact on human health and the environment. Of particular concern are those nanomaterials that exhibit poor excretion and tend to accumulate in living organisms. Our study investigated the potential adverse biological effects of residual gold and titania nanoparticles (PEG-AuNPs and TiO₂NPs) 28 days after a single intravenous administration in rats. To comprehensively assess the potential health hazard of these metal nanoparticles (MNP), toxicological and transcriptomic analyses were employed. The liver was the primary organ of the MNP deposition, causing a reduction in the relative liver weight compared to unexposed animals. Concurrently, changes in serum biomarkers indicative of hepatic dysfunction and hematological and immunological alternations were determined. Integrated transcriptomic analysis unveiled exposure-induced effects on the rats' lungs, liver, and kidneys. The hepatic tissue, particularly in PEG-AuNPs-exposed rats, exhibited a noteworthy prevalence of deregulated genes, with functional classification spanning lipid metabolism, cell cycle, and cell proliferation pathways. Although the number of deregulated miRNAs was relatively modest compared to mRNA expression changes, both types of MNPs deregulated miR-203a, associated with liver injury, and miR-18a-5p and miR-32-5p linked to kidney damage. This study underscores the imperative for a more exhaustive biosafety assessment of poorly soluble MNPs that tend to deposit in the body. Such investigations are crucial for delineating the potential risks of these nanomaterials and guiding the development of adequate safety measures in their production and usage.