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

Chem Res Toxicol. 2015 Oct 19;28(10):1961-74. doi: 10.1021/acs.chemrestox.5b00161. Epub 2015 Oct 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Line
  • Cluster Analysis
  • Ferric Compounds / chemistry*
  • Gene Expression Regulation / drug effects*
  • Hep G2 Cells
  • Humans
  • Magnetite Nanoparticles / chemistry
  • Magnetite Nanoparticles / toxicity*
  • Mice
  • Polyethyleneimine / chemistry
  • Real-Time Polymerase Chain Reaction
  • Succimer / chemistry*


  • Carrier Proteins
  • Ferric Compounds
  • Magnetite Nanoparticles
  • ferric oxide
  • Polyethyleneimine
  • Succimer