| Title: | 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 |
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| Authors: | ID Rozman, Iza (Author)
ID Gallo-Cordova, Álvaro (Author)
ID Puerto Morales, María del (Author)
ID Morales Ovalle, Marco A. (Author)
ID Goya, Gerardo F. (Author)
ID Kološa, Katja (Author)
ID Hočevar, Domen (Author)
ID Žegura, Bojana (Author)
ID Štern, Alja (Author) |
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| Files: |  URL - Source URL, visit https://www.sciencedirect.com/science/article/pii/S0753332225011448?via%3Dihub
 DOCX - Presentation file, download (900,12 KB)
MD5: BD7C88EADDB001B2F4D9E7DF9263350F
 PDF - Presentation file, download (6,14 MB)
MD5: ED6BB33EBBCB684B9EFEF9149CFF6217
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| Language: | English |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: |  NIB - National Institute of Biology
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| Abstract: | 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. |
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| Keywords: | DNA damage, genotoxicity, HepG2 spheroids, magnetic ferrite-based nanoparticles, ROS induction, safety assessment, toxicogenomics |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Publication date: | 06.01.2026 |
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| Year of publishing: | 2026 |
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| Number of pages: | str. 1-15 |
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| Numbering: | Vol. 195, [article no.] ǂ118950 |
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| PID: | 20.500.12556/DiRROS-25695  |
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| UDC: | 577.2 |
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| ISSN on article: | 1950-6007 |
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| DOI: | 10.1016/j.biopha.2025.118950 |
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| COBISS.SI-ID: | 264984323 |
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| Note: | 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;
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| Publication date in DiRROS: | 27.01.2026 |
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| Views: | 47 |
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| Downloads: | 34 |
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