Toxicological assessment of silica-coated iron oxide nanoparticles in human astrocytes

Abstract

Iron oxide nanoparticles (ION) have great potential for an increasing number of medical and biological applications, particularly those focused on nervous system. Although ION seem to be biocompatible and present low toxicity, it is imperative to unveil the potential risk for the nervous system associated to their exposure, especially because current data on ION effects on human nervous cells are scarce. Thus, in the present study potential toxicity associated with silica-coated ION (S-ION) exposure was evaluated on human A172 glioblastoma cells. To this aim, a complete toxicological screening testing several exposure times (3 and 24 h), nanoparticle concentrations (5-100 μg/ml), and culture media (complete and serum-free) was performed to firstly assess S-ION effects at different levels, including cytotoxicity - lactate dehydrogenase assay, analysis of cell cycle and cell death production - and genotoxicity - H2AX phosphorylation assessment, comet assay, micronucleus test and DNA repair competence assay. Results obtained showed that S-ION exhibit certain cytotoxicity, especially in serum-free medium, related to cell cycle disruption and cell death induction. However, scarce genotoxic effects and no alteration of the DNA repair process were observed. Results obtained in this work contribute to increase the knowledge on the impact of ION on the human nervous system cells.

Evaluation of cytotoxicity and genotoxicity induced by oleic acid‐coated iron oxide nanoparticles in human astrocytes

“…In SH‐SY5Y cells, the presence of nanoparticles altered the repair of H 2 O 2 ‐induced DNA damage, with considerably more pronounced effects when serum‐free medium was used (Kiliç et al ). However, results obtained from A172 cells were in accordance with the ones found in the present study, with no alteration in repair ability found at any condition tested (Fernández‐Bertólez et al ). This different response between the two types of nervous system cells are in line with the well‐accepted idea that glial cells may have a more efficient repair ability in order to protect neuronal tissue from external insults (Saeed et al ).…”

“…However, results obtained from A172 cells were in accordance with the ones found in the present study, Environmental and Molecular Mutagenesis. DOI 10.1002/em with no alteration in repair ability found at any condition tested (Fernández-Bertólez et al 2018a). This different response between the two types of nervous system cells are in line with the well-accepted idea that glial cells may have a more efficient repair ability in order to protect neuronal tissue from external insults (Saeed et al 2015).…”

“…Studies addressing the potential effects of ION on cellular repair mechanisms are extremely scarce. Silica‐coated ION effects on repair capacity of SH‐SY5Y and A172 cells were previously assessed by our group by using the same approach (Kiliç et al ; Fernández‐Bertólez et al ). In SH‐SY5Y cells, the presence of nanoparticles altered the repair of H 2 O 2 ‐induced DNA damage, with considerably more pronounced effects when serum‐free medium was used (Kiliç et al ).…”

“…The uptake and intracellular localization of ION in A172 cells were assessed by transmission electron microscopy (TEM) coupled with energy‐dispersive X‐ray spectroscopy (EDX) as previously described (Fernández‐Bertólez et al ). Cells seeded in T25 flasks were exposed to O‐ION dispersed in complete and serum‐free media (25 and 100 μg/mL) for 3 and 24 hr.…”

“…Before carrying out the comet assay experiments, the possible interference between O-ION (at 100 μg/mL, the highest concentration to be tested) and the comet assay methodology was assessed, following Magdolenova et al (2012) recommendations and the protocol described by Fernández-Bertólez et al (2018a). Because no interference was observed in either complete or serumfree media, alkaline comet assay was performed according to the general protocol proposed by Singh et al (1988), with minor changes (Teixeira et al 2010).…”