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. Conclusion: 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.

In vitro inhibition of tumor growth by low-dose iron oxide nanoparticles activating macrophages

“…Many studies have found that high doses of nanoparticles reduce cell viability, generate reactive oxygen species, induce inflammation, differentiation, apoptosis, and damage DNA. 31 However, low doses of nanoparticles may stimulate the cellular responses. 32 Among three main different cell types of freely circulating immune cells (phagocytes, amoebocytes, and vibratile cells), 1 µg/mL of TiO 2 nanoparticles produced an 10% increase in the relative number of phagocytes ( P = 0.01).…”

Gene Expression and Transcriptome Profiling of Changes in a Cancer Cell Line Post-Exposure to Cadmium Telluride Quantum Dots: Possible Implications in Oncogenesis

“…67 Interestingly, several pathways related to viral infection (virus entry via the endocytic pathway and hepatic fibrosis pathway) were significantly enriched by the DEGs, and have also been reported to be active in neurotoxicity in rats 8 and cells exposed to iron nanoparticles. 20,68 Based on the gene expression pattern observed in the gene interaction and network analysis, it appears that genes responsible for induction of the immune response, cell adhesion and migration, type I interferon signaling pathway, cell proliferation, endoplasmic reticulum stress, and unfolded protein response were significantly induced. These biological and cellular processes are required for cancer development and tumorigenesis.…”

“…17 As such, it is pertinent to investigate the mechanisms of QD cytotoxicity. Indeed, to assess the global effect of nanoparticles on target cells, transcriptomic profiling has been undertaken in several studies, as in the case of silver and titanium nanoparticles, 18 genotoxic and non-genotoxic carcinogens, 19 11-nm dimercaptosuccinic acid-coated magnetite nanoparticles, 20 and for fibroblasts. 21 The aim of this study is thus to investigate the effects of CdTe-QD exposure in Chang cancer cells via microarray gene expression profiling to explore their oncogenic potential in terms of causing a more aggressive form of cancer.…”

“…17 As such, it is pertinent to investigate the mechanisms of QD cytotoxicity. Indeed, to assess the global effect of nanoparticles on target cells, transcriptomic profiling has been undertaken in several studies, as in the case of silver and titanium nanoparticles, 18 genotoxic and non-genotoxic carcinogens, 19 11-nm dimercaptosuccinic acid-coated magnetite nanoparticles, 20 and for fibroblasts. 21…”

Gene interfered-ferroptosis therapy for cancers

“…The DMSA-coated Fe 3 O 4 magnetic nanoparticle (FeNP) were provided by the Biological and Biomedical Nanotechnology Group of the State Key Lab of Bioelectronics, Southeast University, Nanjing, China 56 . This FeNP was characterized by our previous study 36,[57][58][59][60] . A magnetic transfection agent (MagTransf TM ) was purchased from the Nanjing Nanoeast Biotech co., ltd (Nanjing, China), which was referred to as FeNC in this study.…”