Progressive lysosomal membrane permeabilization induced by iron oxide nanoparticles drives hepatic cell autophagy and apoptosis.
Kateryna LevadaStanislav PshenichnikovAlexander OmelyanchikValeria RodionovaAleksey NikitinAlexander SavchenkoIgor SchetininDmitry ZhukovMaxim AbakumovAlexander MajougaMariia LunovaMilan JirsaBarbora SmolkováMariia UzhytchakAlexandr DejnekaOleg LunovPublished in: Nano convergence (2020)
Iron oxide nanoparticles (IONs) are frequently used in various biomedical applications, in particular as magnetic resonance imaging contrast agents in liver imaging. Indeed, number of IONs have been withdrawn due to their poor clinical performance. Yet comprehensive understanding of their interactions with hepatocytes remains relatively limited. Here we investigated how iron oxide nanocubes (IO-cubes) and clusters of nanocubes (IO-clusters) affect distinct human hepatic cell lines. The viability of HepG2, Huh7 and Alexander cells was concentration-dependently decreased after exposure to either IO-cubes or IO-clusters. We found similar cytotoxicity levels in three cell lines triggered by both nanoparticle formulations. Our data indicate that different expression levels of Bcl-2 predispose cell death signaling mediated by nanoparticles. Both nanoparticles induced rather apoptosis than autophagy in HepG2. Contrary, IO-cubes and IO-clusters trigger distinct cell death signaling events in Alexander and Huh7 cells. Our data clarifies the mechanism by which cubic nanoparticles induce autophagic flux and the mechanism of subsequent toxicity. These findings imply that the cytotoxicity of ION-based contrast agents should be carefully considered, particularly in patients with liver diseases.
Keyphrases
- cell death
- cell cycle arrest
- iron oxide nanoparticles
- magnetic resonance imaging
- iron oxide
- magnetic resonance
- oxidative stress
- induced apoptosis
- endothelial cells
- electronic health record
- multiple sclerosis
- poor prognosis
- contrast enhanced
- pi k akt
- high resolution
- big data
- high glucose
- cell therapy
- cell proliferation
- bone marrow
- binding protein
- mesenchymal stem cells
- long non coding rna
- water soluble
- photodynamic therapy
- stress induced