Degradation of Superparamagnetic Iron Oxide Nanoparticle-Induced Ferritin by Lysosomal Cathepsins and Related Immune Response

AIM: To examine the physiological impact of superparamagnetic iron oxide nanoparticles (SPIONs) on cell function and its interaction with oxysterol laden cells. MATERIALS & METHODS: Intracellular iron was determined by Prussian blue staining. Cellular ferritin, cathepsin L and ferroportin were analyzed by flow cytometry and fluorescence microscopy. Cytokine secretion was determined by ELISA and immunoblotting. RESULTS: In U937 and THP 1 cells, we did not detect any loss of cell viability on SPION loading. Desferrioxamine prevents induction of both ferritin and cathepsin L by SPIONs. Inhibition of lysosomal cathepsins upregulates both endogenous- and SPION-induced ferritin. SPION loading induces membranous ferroportin and incites secretion of ferritin, TNF-α and IL-10. 7β-hydroxycholesterol exposure reduces SPION uptake by cells. CONCLUSION: SPION loading results in upregulation of lysosomal cathepsin, membranous ferroportin and ferritin degradation, which is associated with secretion of both pro- and anti-inflammatory cytokines. A reduced SPION uptake by oxysterol-laden cells may lead to a compromised MRI with elevated cathepsins and ferritin.