This study investigated the cell apoptosis and gene expression profiles of human THP-1 monocytes in order to identify the molecular mechanism of cell apoptosis induced by meso-2,-3-dimercaptosuccinnic acid-coated Fe3O4magnetic nanoparticles. Cell apoptosis was visualized with flow cytometry after treated by 50 and 100 μg/ml Fe3O4nanoparticles, and the gene expression profiles were detected with Affymetrix Human Genome U133 Plus 2.0 GeneChips® microarrays. The transmission electron microscopy obserbation revealed that THP-1 cells were effectively labeled by the Fe3O4nanoparticles. The internalized Fe3O4nanoparticles increased cell apoptosis in a dose-dependent manner, but not decreased cell viability significantly. The cDNA microarray results showed that hundreds of genes were significantly regulated at the concentration of 50 and 100 μg/ml, and the level of these genes exhibited a dose response, includingCD14,CD86,CFLAR,IL-1,NFKBIA,NLRC4,NAIPandAIP3. The Fe3O4nanoparticles treatments resulted in significantly altered in Toll-like receptor signaling pathway, NOD-like receptor signaling pathway, and Cell apoptosis signaling pathway. Gene ontology analysis of these differentially expressed genes demonstrated that mainly up-regulated genes were related to cytokine production and cell apoptosis. These results showed that the Fe3O4nanoparticles induced THP-1 cells apoptosis and the level of lots of genes involved in extrinsic apoptosis pathway differentially expressed, which further revealed demonstrated the relation between Fe3O4MNPs treatment and cell apoptosis.
