Toxicity and biodegradation of zinc ferrite nanoparticles in Xenopus laevis

Abstract

Zn-doped Fe3O4 magnetic nanoparticles have been proposed as the ideal ferrite for some biomedical applications like magnetic hyperthermia or photothermal therapy because of the possibility to adjust their size and chemical composition in order to design tailored treatments. However, reliable approaches are needed to risk assess Zn ferrite nanoparticles before clinical development. In this work, the in vitro toxicity of the nanoparticles was evaluated in five cellular models (Caco-2, HepG2, MDCK, Calu-3 and Raw 264.7) representing different target organs/systems (gastrointestinal system, liver, kidney, respiratory system and immune system). For the first time, these nanoparticles were evaluated in an in vivo Xenopus laevis model to study whole organism toxicity and their impact on iron and zinc metabolic pathways. Short and long-term in vivo exposure studies provided insights into the contrasting adverse effects between acute and chronic exposure. Quantitative PCR combined with elemental analysis and AC magnetic susceptibility measurements revealed that at short-term exposure (72 h) the nanoparticles' absorption process is predominant, with the consequent over-expression of metal transporters and metal response proteins. At long-term exposure (120 h), there is an up-regulation of 2 metal accumulation involved genes and the return to basal levels of both iron and zinc transporters, involved in the uptake of metals. This suggests that at this stage the nanoparticles' absorption process is residual compared with the following steps in metabolism, distribution and/or excretion processes, indicated by the increase of iron accumulation proteins at both transcriptional and translational level. This testing approach based on a battery of cellular systems and the use of the Xenopus laevis model could be a viable strategy for studying the toxicity, degradability and ultimately the long-term fate of zinc ferrites in the organism.

Iron Speciation in Animal Tissues Using AC Magnetic Susceptibility Measurements: Quantification of Magnetic Nanoparticles, Ferritin, and Other Iron-Containing Species

“…This fingerprint signal was in agreement with previously described results for mouse ferritin measured in similar conditions and for ferritin from other mammals such as rats or horses . Indeed, similar signals, located at slightly lower temperatures have also been described for ferritins coming from Xenopus laevis or Drosophila melanogaster …”

Di- and tri-component spinel ferrite nanocubes: synthesis and their comparative characterization for theranostic applications

“…Comparing our viability results with previous studies in which mixed ferrite nanoparticles were employed is not straightforward, because often, the nanoparticles chosen for those studies differ in size, composition, shape and coatings, all parameters affecting nanoparticle behavior in cell media thus their cytotoxicity on chosen cancer cell lines. [65][66][67][68] The cell viability findings with our Zn-ferrite NCs are in line with Zn-ferrite nanoparticles prepared by the electrochemical method, with a spherical shape, similar size (13 nm) and similar non-stoichiometry composition (Zn 0.5 Fe 2.5 O 4 ), and administered at a similar nanoparticle dosage. 65 For the Co-ferrite NCs, at 100 nM and after 72 h, the cell morphology looked altered, with membrane blabbing and clear signs of cell suffering.…”

Potential Toxicity of Iron Oxide Magnetic Nanoparticles: A Review

“…In the in vivo study, abnormal phenotypes were identified, with swollen and deformed gastrointestinal tracts. At short term exposure of 72 h predominant absorption of NPs was observed, with overexpression of metal response proteins and metal transporters, whereas after long term exposure of 120 h the upregulated genes involved in metal accumulation returned to basal levels for both iron and zinc in the body, which primarily suggests that at the long term exposure stage, the nanoparticle absorption process is much less because of underlying processes of metabolism, distribution and excretion [ 152 ].…”