Absorption mechanism of iron oxide nanoparticles in Caco-2 cell model
OBJECTIVE To explore the possible mechanism of absorption of iron oxide nanoparticles into the human body through the gastrointestinal tract.METHODS Th is article used Caco-2 monolayer cells as a cell model,prepared characterized iron oxide nanoparticles(Fe2O3 NPs)as suspensions,and intervened in Caco-2 cells.CCK-8 method,transwell method,and atomic spectrophotometer method were used to explore the effect of Fe2O3 NPs on the activity of Caco-2 cells and the absorption and transport of them through the Caco-2 monolayer cell model.After treating Caco-2 cells with different doses of iron oxide nanoparticles suspension,electron microscopy observation and endocytosis inhibitors(chlorpromazine,methyl-β-cyclodextrin,amiloride)and western blot were performed exploring the absorption mechanism of iron oxide nanoparticles on Caco-2 cells.RESULTS 1.5,1.0 and 0.5 mg/mL were selected as absorption mechanism studies and exposure doses based on cell activity and absorption transport test result.Under electron microscopy,Fe2O3 NPs were distributed both inside and outside the cell.Fe2O3 NPs presented in the cytoplasm and vesicular like structures within cells.Endocytosis inhibitors chlorpromazine and methyl-β-cyclodextrin treatment for 24 hours showed inhibitory effects on the absorption of Fe2O3 NPs in the Caco-2 cell model.Treatment of Caco-2 cells with Fe2O3 NPs could increase the expression of divalent metal transporter(DMT1)and ferroportin 1(FPN1)(P＜0.01),while decreasing expression of occludin(P＜0.05).CONCLUSION There are three absorption mechanisms of iron oxide nanoparticles on Caco-2 cells:endocytosis pathways mediated by reticulin and caveolin/lipid raft proteins,absorption and transport involving iron transport related proteins,and paracellular pathways accompanied by the disruption of tight junction proteins.
iron oxide nanoparticlesCaco-2 cellsabsorption mechanism
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