20.500.12556/DiRROS-25695 Safety of ferrite nanoparticles for biomedical applications: cyto- and genotoxic effects of MxFe3-xO4 (M = Fe, Zn, Mn) in an advanced 3D human hepatic in vitro model Given the growing interest in nanosized spinel-type ferrite nanoparticles for biomedical applications and the limited information on their safety, this study aimed to assess their cellular and genotoxic effects in an in vitro 3D human hepatic cell model (HepG2 spheroids). Ferrite nanoparticles – γFe2O3 (FeNPs; 14 ± 4 nm), Zn0.7Fe2.3O4 (ZnNPs; 14 ± 5 nm), and Mn0.4Fe2.6O4 (MnNPs; 7 ± 2 nm) – were synthesised through a microwave-assisted polyol route, functionalized with citric acid, and characterised using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES), Transmission Electron Microscopy (TEM), X-ray Diffraction (XRD), and Fourier Transform Infrared Spectroscopy (FTIR). Nanoparticle uptake was analysed using TEM, cytotoxicity was measured with CellTiter-Glo®, and oxidative stress induction was assessed using the 2′,7′-Dichlorodihydrofluorescein diacetate (DCFH-DA) and malondialdehyde (MDA) assay. Genotoxic effects were evaluated using the comet, γH2AX and p-H3 assays. Cellular stress responses were assessed using toxicogenomic analysis. Significant cytotoxicity of the tested nanoparticles (0.1–250 µg/mL) was observed; however, TEM analysis revealed limited penetration to the outermost cell layers of spheroids. Notably, only FeNPs induced ROS generation, while MDA levels remained unchanged in all tested samples. Low DNA damage was detected at 24 h, but a significant increase was observed at 96 h (5–50 µg/mL). No increase in γH2AX or p-H3 was found. No substantial alterations in DNA damage or oxidative stress-response gene expression were detected. Altogether, our findings suggest that the effects of ferrite nanoparticles are time- and composition-dependent, underlining the importance of further mechanistic and chronic exposure evaluations in 3D cell models. DNA damage genotoxicity HepG2 spheroids magnetic ferrite-based nanoparticles ROS induction safety assessment toxicogenomics poškodba DNK genotoksičnost HepG2 sferoidi magnetni nanodelci na osnovi ferita indukcija ROS ocena varnosti toksikogenomika true false true Angleški jezik Slovenski jezik Neznano 2026-01-27 13:13:51 2026-01-27 13:13:51 2026-01-28 04:15:08 0000-00-00 00:00:00 2026 0 0 Nasl. z nasl. zaslona; Soavtorji: Alvaro Gallo-Cordova, María del Puerto Morales, Marco A. Morales Ovalle, Gerardo F. Goya, Katja Kološa, Domen Hočevar, Bojana Žegura, Alja Štern; Opis vira z dne 16. 1. 2026; str. 1-15 [article no.] ǂ118950 Vol. 195 2026 0000-00-00 Zaloznikova Objavljeno apc 0000-00-00 0000-00-00 2026-01-06 577.2 1950-6007 10.1016/j.biopha.2025.118950 264984323 https://www.sciencedirect.com/science/article/pii/S0753332225011448?via%3Dihub 1 a783a17f-fb79-11f0-a15d-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=39004 1-s2.0-S0753332225011448-mmc1.docx 1-s2.0-S0753332225011448-mmc1.docx 1 BD7C88EADDB001B2F4D9E7DF9263350F f165c2b85f9e8b87b000104b98cf6f9350ce974f69012ed1f2791179b3f254d5 c9b8c654-fb79-11f0-a15d-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=39005 RAZ_Rozman_Iza_2026.pdf RAZ_Rozman_Iza_2026.pdf 1 ED6BB33EBBCB684B9EFEF9149CFF6217 cf068a056b4fa506029f6fb0b90d36c6c94e09070880855c3e849199f63af5cb d37397ed-fb79-11f0-a15d-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=39006 Nacionalni inštitut za biologijo Transcriptomic responses of oxidative and genotoxic stress responsive genes after exposure to MxFe3-xO4 (M = Fe, Zn, Mn) in an advanced 3D human hepatic in vitro model TEM images of HepG2 spheroids exposed to magnetic Ferite-based Nanoparticles MxFe3-xO4 (M=Fe, Zn, Mn) for 24 and 96 hours 0 0 0