Cellular mechanisms of transcriptional regulation of human cell lines exposed to cadmium-based quantum dots

Abstract

In recent years, the interest in quantum dots (QDs) has spread across different branches of biology and medicine thanks to their photophysical properties, which make them excellent candidates for use in bioimaging, drug delivery, theranostic applications and, more recently, gene therapy. With the continuous expansion of applications, QD-mediated cellular responses have become of concern. The immune system and the liver have been confirmed to be important targets, and both are sensitive to cadmium sulfide quantum dots (CdS QDs). Here, the effect on mRNA has been studied by whole-transcriptome analysis in human HepG2 cells (as a model of liver cells) and THP-1 macrophage-like cells, and the mechanisms of mRNA regulation by miRNAs during exposure to Cd as CdS QDs or Cd(II) (as CdSO₄ 8/3-hydrate) are discussed. CdS QD exposure induced modulation of the transcriptome of hepatocytes activating RAS signaling and increasing intracellular calcium, which results in the activation of the apoptotic pathway. CdS QDs also affect macrophages inducing production of TNFα and other cytokines and hindering the autophagic process. The results obtained in vitro on mRNA regulation are partially consistent with those hypothesized after in silico analysis of a wide range of miRNAs regulated in the same conditions.