DMSA-Coated Iron Oxide Nanoparticles Greatly Affect the Expression of Genes Coding Cysteine-Rich Proteins by Their DMSA Coating

The
dimercaptosuccinic acid (DMSA) was widely used to coat iron oxide
nanoparticles (FeNPs); however, its intracellular cytotoxicity remains
to be adequately elucidated. This study analyzed the differentially
expressed genes (DEGs) in four mammalian cells treated by a DMSA-coated
magnetite FeNP at various doses at different times. The results revealed
that about one-fourth of DEGs coded cysteine-rich proteins (CRPs)
in all cells under each treatment, indicating that the nanoparticles
greatly affected the expressions of CRP-coding genes. Additionally,
about 26% of CRP-coding DEGs were enzyme genes in all cells, indicating
that the nanoparticles greatly affected the expression of enzyme genes.
Further experiments with the nanoparticles and a polyethylenimine
(PEI)-coated magnetite FeNP revealed that the effect mainly resulted
from DMSA carried into cells by the nanoparticles. This study thus
first reported the cytotoxicity of DMSA at the gene transcription
level as coating molecules of FeNPs. This study provides new insight
into the molecular mechanism by which the DMSA-coated nanoparticles
resulted in the transcriptional changes of many CRP-coding genes in
cells. This study draws attention toward the intracellular cytotoxicity
of DMSA as a coating molecule of nanoparticles, which has very low
toxicity as an orally administered antidote due to its extracellular
distribution.