title: Effects of an 11-nm DMSA-coated iron nanoparticle on the gene expression profile of two human cell lines, THP-1 and HepG2.
abstract: BACKGROUND
  Iron nanoparticles (FeNPs) have attracted increasing attention over the past two decades owing to their promising application as biomedical agents. However, to ensure safe application, their potential nanotoxicity should be carefully and thoroughly evaluated. Studies on the effects of FeNPs on cells at the transcriptomic level will be helpful for identifying any potential nanotoxicity of FeNPs and providing valuable mechanistic insights into various FeNPs-induced nanotoxicities.
  
  
  RESULTS
  This study investigated the effects of an 11-nm dimercaptosuccinic acid-coated magnetite nanoparticle on the gene expression profiles of two human cell lines, THP-1 and HepG2. It was found that the expression of hundreds of genes was significantly changed by a 24-h treatment with the nanoparticles at two doses, 50 μg/mL and 100 μg/mL, in the two cell types. By identifying the differentially expressed genes and annotating their functions, this study characterized the general and cell-specific effects of the nanoparticles on two cell types at the gene, biological process and pathway levels. At these doses, the overall effects of the nanoparticle on the THP-1 cells were the induction of various responses and repression of protein translation, but in the HepG2 cells, the main effects were the promotion of cell metabolism, growth and mobility. In combination with a previous study, this study also characterized the common genes, biological processes and pathways affected by the nanoparticle in two human and mouse cell lines and identified Id3 as a nanotoxicity biomarker of the nanoparticle.
  
  
  CONCLUSIONS
  The studied FeNPs exerted significant effects on the gene expression profiles of human cells. These effects were highly dependent on the innate biological functions of cells, i.e., the cell types. However, cells can also show some cell type-independent effects such as repression of Id3 expression. Id3 can be used as a nanotoxicity biomarker for iron nanoparticles.
authors.affiliation: State Key Laboratory of Bioelectronics, Southeast University, Nanjing, 210096, China. lovegoflying@163.com.|School of Biomedical Engineering, Hubei University of Science and Technology, Xianning, 437000, China. lovegoflying@163.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Bioelectronics, Southeast University, Nanjing, 210096, China. wangxintsxy@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Bioelectronics, Southeast University, Nanjing, 210096, China. zoujinglu2008@163.com.
authors.forename: Jinglu
authors.initials: J
authors.lastname: Zou
authors.affiliation: State Key Laboratory of Bioelectronics, Southeast University, Nanjing, 210096, China. liuyingxiong@seu.edu.cn.
authors.forename: Yingxun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Bioelectronics, Southeast University, Nanjing, 210096, China. wangjinke@seu.edu.cn.
authors.forename: Jinke
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002460:Cell Line / Q000187:drug effects; D016000:Cluster Analysis; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics; D007501:Iron / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D058185:Magnetite Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D051379:Mice; D058977:Molecular Sequence Annotation; D009363:Neoplasm Proteins / Q000235:genetics; D004113:Succimer / Q000737:chemistry*; D018675:Toxicity Tests / Q000379:methods; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D051796:Inhibitor of Differentiation Proteins; D058185:Magnetite Nanoparticles; D009363:Neoplasm Proteins; C075640:ID3 protein, human; D004113:Succimer; D007501:Iron