Evaluation of the uptake, storage and cell effects of nano-iron in enterocyte-like cell models

The therapy with nanocompounds is widely used to treat Fe deficiency and an emerging trend to inhibit tumor growth. The present work aims to address the management of different FeONP, comparing sucrose covered FeONP and Fe nanoparticles in the form of the ferritin with non-particulated inorganic Fe (II) by enterocytes-like colon cancer cell lines (Caco-2 and HT-29). Iron uptake results revealed significantly higher Fe incorporation in the case of nanoparticulated Fe, first in the form of FeONP and second in the form of ferritin with respect to inorganic Fe (II). Furthermore, the intracellular Fe fractionation, conducted by size exclusion chromatography coupled on line to inductively coupled plasma mass spectrometry (SEC-ICP-MS) showed a significant increase of the Fe-ferritin peak upon exposure of cells to the following compounds ferritin > FeONP > FeSO_4. Such results point out that the sucrose coated FeONP released Fe into the cell cytosol that was used to replenish the existing cytosolic ferritin without inducing changes in the protein concentration. On the other hand, the increase of the Fe-ferritin peak in cells exposed to ferritin as iron source is due to a significant increase on the intracellular protein concentration, as proved by using an ICP-MS linked ferritin sandwich immune assay. Cell viability experiments conducted with concentrations up to 1000 μmol L^-1 (as Fe) of each compound under scrutiny did not reveal significant differences among Fe species regarding global cellular toxicity. However, significant cell DNA damage was detected when treating the cells with FeONP (500 μmol L^-1).