Glucose coated FeO@Fe3O4 nanoparticles show tunable catalytic reactivity and safety in a 3D hepatic in vitro modelMorales Ovalle, Marco A. (Avtor) Rozman, Iza (Avtor) Winkler, Elin L. (Avtor) Lima, Enio (Avtor) Štern, Alja (Avtor) Kološa, Katja (Avtor) Žegura, Bojana (Avtor) Goya, Gerardo F. (Avtor) iron-oxide nanoparticlesFenton-like catalysiscytotoxicitygenotoxicityHepG2 spheroidsIron-oxide magnetic nanoparticles (MNPs) have been extensively investigated as magnetically actuated nanocatalysts for diagnostic and therapeutic applications. However, because wüstite/magnetite/maghemite phases can interconvert, coexisting Fe2+/Fe3+ species may redirect Fenton-like chemistry and generate reactive oxygen species (ROS) profiles that differ from the intended biocatalytic pathway. Here, we investigate monodisperse biphasic FeO@Fe3O4 core-shell MNPs with an average particle size ⟨d⟩ = 9.6(5) nm, and their glucose-coated analogue, combining EPR radical analysis with toxicity testing in a 3D HepG2 hepatic spheroid model. Naked particles exhibited conventional Fenton-like behavior dominated by hydroxyl radicals (⋅OH), whereas glucose coating markedly suppressed ⋅OH while increasing hydroperoxyl radicals (⋅OOH; ≈55 pM at 60 min), demonstrating ligand-controlled rerouting of the radical pathway. TEM mapping across spheroid cross-sections showed preferential MNP accumulation in the outer layer, with most observed events confined to the outer ≈10–15 μm, corresponding to an approximately one-cell-thick rim; sparse deeper events were observed up to ≈30–35 μm. MNPs produced dose- and time-dependent cytotoxicity in HepG2 spheroids, with IC50 values of 29.3 (24 h) and 10.8 (96 h) µg·cm− 2, without evidence of lipid peroxidation or genotoxicity. MDA levels remained unchanged, the comet assay showed no increase in DNA damage, and γH2AX and phospho-H3 (p-H3) positive events were not detected. Our results show that glucose functionalization provides a simple route to modulate radical pathways and define operational windows for redox-active FeO@Fe3O4 nano-reactors in oxidative nanomedicine.20262026-06-02 14:02:23Neznano29663sl