Stress reaction of kidney epithelial cells to inorganic solid-core nanoparticles

Abstract

A route of accumulation and elimination of therapeutic engineered nanoparticles (NPs) may be the kidney. Therefore, the interactions of different solid-core inorganic NPs (titanium-, silica-, and iron oxide-based NPs) were studied in vitro with the MDCK and LLC-PK epithelial cells as representative cells of the renal epithelia. Following cell exposure to the NPs, observations include cytotoxicity for oleic acid-coated iron oxide NPs, the production of reactive oxygen species for titanium dioxide NPs, and cell depletion of thiols for uncoated iron oxide NPs, whereas for silica NPs an apparent rapid and short-lived increase of thiol levels in both cell lines was observed. Following cell exposure to metallic NPs, the expression of the tranferrin receptor/CD71 was decreased in both cells by iron oxide NPs, but only in MDCK cells by titanium dioxide NPs. The tight association, then subsequent release of NPs by MDCK and LLC-PK kidney epithelial cells, showed that following exposure to the NPs, only MDCK cells could release iron oxide NPs, whereas both cells released titanium dioxide NPs. No transfer of any solid-core NPs across the cell layers was observed.

Towards an alternative testing strategy for nanomaterials used in nanomedicine: Lessons from NanoTEST

“…The internalization of NPs is highly sizedependent; however, uptake might not follow commonly defined size limits, and kinetics of uptake for the same type of NPs varies in the different cell types (dos Santos et al, 2011). NP transport is most affected by tightness of the cell barrier, with transport increasing in the order: brain5placenta5kidney after 2 h and brain5kidney5placenta after 24 h exposure as shown from transport studies of OC-Fe 3 O 4 NPs utilising different cell types (Figure 1; Correia Carreira et al, 2015;Halamoda Kenzaoui et al, 2012a, 2013b. The different order in extent of transport with time is likely to be due to changes in cell growth in each model and will reflect differences in the tightness of the barrier formed.…”

“…In vitro experiments with cells representing different organ targets revealed that oxidative stress and toxic effects induced by NPs depend on the NPs' properties, the test used and the cell type. Polylactic-coglycolic acid (PLGA-PEO) NPs induced little or no oxidative stress in any cell type compared with solid-core metallic NPs which generally produced ROS (Guadagnini et al, 2015b;Halamoda Kenzaoui et al, 2012c, 2013b. Genotoxicity induced by NPs depends on the NPs, the dispersion protocol and the measured endpoint (Magdolenova et al, 2012a).…”

Transfer of Ultrasmall Iron Oxide Nanoparticles from Human Brain-Derived Endothelial Cells to Human Glioblastoma Cells

“…For cell viability and DNA synthesis, cells were grown in 48-well cell culture plates (Costar, Corning, NY, USA) until 75% confluent and exposed to the USPIO NPs in complete culture medium for the concentration and time indicated, then washed in saline (0.9% NaCl (w/v)). Cell viability was evaluated using the MTT assay, essentially as previously described . DNA synthesis was determined by tritiated thymidine ( 3 H-T) incorporation, essentially as previously described .…”

“…Cells were grown in 48-well plates until 75% confluent, then exposed to the USPIO NPs for the concentration and time indicated. Then, cell-associated iron content was quantified by the soluble Prussian Blue reaction, essentially as previously described . Briefly, for quantitative iron determination, the cell layers were dissolved in 6 N HCl, then a 5% solution of K 4 [Fe(CN) 6 ]·3H 2 O (Merck, VWR international, Nyon, Switzerland) in H 2 O was added for 10 min and the absorbance was measured at 690 nm in a multiwell plate reader (iEMS Labsystems).…”

“…Such an achievement would involve the transport of the nanoparticulate therapeutics, from the luminal to the basolateral sides of the brain vascular system across the endothelial cells, if such a transport system can be designed. Ultrasmall superparamagnetic iron oxide nanoparticles (USPIO NPs) are particularly promising devices since their magnetic properties increase the number of possible applications in many areas of the biomedical field, including drug delivery, thermotherapy, imaging and detection of cancer. , However, their potential and pathways to cross biological barriers, including the blood–brain barrier (BBB) and the blood–brain tumor barrier (BBTB) needs to be confirmed if they are to be used in the diagnosis and therapy of brain diseases and brain tumors. − Previous studies, including ours, have addressed the translocation of NPs of various compositions across cell layers using two-compartments devices separated by a polymeric membrane, but these previous studies have used only one type of cells and did not demonstrate a very efficient transport, possibly because of the characteristics of the polymeric membrane separating the two compartments. − Only one previous study has suggested, using a three-cell coculture model of the lung including epithelial cells, macrophages and dendritic cells, that macrophages and dendritic cells can exchange 1 μm polystyrene NPs via cell extended cytoplasmic processes across the epithelial layer. However, these cells belong to the immune phagocytic lineage and the mechanisms involved need to be defined.…”