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Iron oxide nanoparticles trigger endoplasmic reticulum damage in steatotic hepatic cells

Mariia Uzhytchak, Mariia Lunová, Barbora Smolková, M Jirsa, A. Dejneka, Oleg Lunov

2023Nanoscale Advances11 citationsDOIOpen Access PDF

Abstract

models. In this study, we demonstrate that IONPs, at a dose that does not cause general toxicity in hepatic cells (Alexander and HepG2), induce significant toxicity in steatotic cells (cells loaded with non-toxic doses of palmitic acid). Mechanistically, co-treatment with PA and IONPs resulted in endoplasmic reticulum (ER) stress, accompanied by the release of cathepsin B from lysosomes to the cytosol. The release of cathepsin B, along with ER stress, led to the activation of apoptotic cell death. Our results suggest that it is necessary to consider the interaction between IONPs and the liver, especially in susceptible livers. This study provides important basic knowledge for the future optimization of IONPs as MRI contrast agents for various biomedical applications.

Topics & Concepts

Endoplasmic reticulumIron oxide nanoparticlesCytosolChemistryCell biologyNanoparticleCathepsin DBiochemistryBiophysicsBiologyMaterials scienceNanotechnologyEnzymeEndoplasmic Reticulum Stress and DiseaseIron Metabolism and DisordersErythrocyte Function and Pathophysiology