[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: This article used Caco-2 monolayer cells as a cell model, prepared characterized iron oxide nanoparticles(Fe_2O_3 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 Fe_2O_3 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, Fe_2O_3 NPs were distributed both inside and outside the cell. Fe_2O_3 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 Fe_2O_3 NPs in the Caco-2 cell model. Treatment of Caco-2 cells with Fe_2O_3 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.