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Toxicity of Magnetic Nanoparticles in Medicine: Contributing Factors and Modern Assessment Methods

Nowak-Jary, Julia, Machnicka, Beata·2025·International Journal of Molecular Sciences
DOI 10.3390/ijms26178586PMC PMC12428864
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Abstract

With the rapid evolution of nanotechnology, magnetic iron oxide nanoparticles (MNPs)—primarily Fe3O4 and γ-Fe2O3—have gained prominence in biomedicine. Their extensive specific surface area, tunable surface functionalities, and intrinsic magnetic characteristics render them highly versatile for diverse clinical applications, including tumor visualization through Magnetic Resonance Imaging (MRI), radiolabeling, targeted radiotherapy, hyperthermia, gene transfer, drug delivery, Magnetic Particle Imaging (MPI), magnetic blood filtration and theranostic strategies. Nevertheless, ensuring the biocompatibility and non-toxicity of these nanostructures remains a fundamental prerequisite for their medical implementation. Hence, it is essential to continuously refine our understanding of MNP-related toxicity and pursue comprehensive research on this front. This article consolidates up-to-date insights into the evaluation of MNPs’ toxicological profiles, emphasizing the influence of physicochemical properties such as morphology, surface modifications, and electrostatic characteristics, along with operational factors like dosage and administration routes. Traditional toxicity testing strategies, including in vitro assays as first-line screening tools, together with standard ex vivo and in vivo models, are discussed. Special attention is given to the emerging role of New Approach Methodologies (NAMs), such as organoid formation, 3D bioprinting, in ovo chicken embryo assays, and image cytometry. These techniques offer ethical, human-relevant, and informative alternatives to animal testing, supporting more predictive and translationally relevant toxicity assessment of MNPs. Taken together, the integration of conventional assays with innovative NAMs, alongside careful consideration of physicochemical and operational factors, is essential to translate the laboratory promise of MNPs into safe and clinically effective nanomedicines.

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Figure 1 The main factors influencing the toxicity of MNPs. Several physicochemical and experimental determinants govern the biological effects of magnetic nanoparticles, including particle size, shape, surface charge, and coating molecules, as well as the route and regimen of administration. These parameters can significantly modulate cellular uptake, biodistribution, and the extent of toxic responses, thereby determining the overall safety profile of MNPs in biomedical applications. Created in Biorender. Julia Nowak-Jary. (2025) https://BioRender.com/ (accessed on 29 July 2025).
Figure 1 The main factors influencing the toxicity of MNPs. Several physicochemical and experimental determinants govern the biological effects of magnetic nanoparticles, including particle size, shape, surface charge, and coating molecules, as well as the route and regimen of administration. These parameters can significantly modulate cellular uptake, biodistribution, and the extent of toxic responses, thereby determining the overall safety profile of MNPs in biomedical applications. Created in Biorender. Julia Nowak-Jary. (2025) https://BioRender.com/ (accessed on 29 July 2025).CC BY · PubMed Central
Figure 2 Methods and representative assays used for the evaluation of MNPs toxicity. Toxicological assessment of magnetic nanoparticles relies on a broad spectrum of complementary strategies, including in vitro assays (e.g., tetrazolium-based viability assays, LDH release, NRU (neutral red uptake assay), ROS measurement, genotoxicity and immunotoxicity tests), ex vivo techniques (histology and histopathology), in vivo models (blood biochemistry and hematological analysis), as well as in ovo approaches (e.g., CAM assay, comet assay, hemolysis, oxidative stress evaluation). Together, these methods provide a comprehensive view of MNP-induced biological responses at cellular, tissue, and organismal levels. Created in Biorender. Julia Nowak-Jary. (2025) https://BioRender.com/ (accessed on 29 July 2025).
Figure 2 Methods and representative assays used for the evaluation of MNPs toxicity. Toxicological assessment of magnetic nanoparticles relies on a broad spectrum of complementary strategies, including in vitro assays (e.g., tetrazolium-based viability assays, LDH release, NRU (neutral red uptake assay), ROS measurement, genotoxicity and immunotoxicity tests), ex vivo techniques (histology and histopathology), in vivo models (blood biochemistry and hematological analysis), as well as in ovo approaches (e.g., CAM assay, comet assay, hemolysis, oxidative stress evaluation). Together, these methods provide a comprehensive view of MNP-induced biological responses at cellular, tissue, and organismal levels. Created in Biorender. Julia Nowak-Jary. (2025) https://BioRender.com/ (accessed on 29 July 2025).CC BY · PubMed Central
Figure 3 Conceptual diagram illustrating the main stages of 3D bioprinting of the organ: (a) computational design, (b) bioink preparation, (c) 3D printing of the organ, (d) functional maturation of the tissue. Created with Ideogram.ai. https://ideogram.ai/t/my-images (accessed on 29 July 2025).
Figure 3 Conceptual diagram illustrating the main stages of 3D bioprinting of the organ: (a) computational design, (b) bioink preparation, (c) 3D printing of the organ, (d) functional maturation of the tissue. Created with Ideogram.ai. https://ideogram.ai/t/my-images (accessed on 29 July 2025).CC BY · PubMed Central
Figure 4 Organoid generation through guided self-organization and tissue-specific differentiation. Created in Biorender.com. Julia Nowak-Jary. (2025) https://BioRender.com/ (accessed on 29 July 2025).
Figure 4 Organoid generation through guided self-organization and tissue-specific differentiation. Created in Biorender.com. Julia Nowak-Jary. (2025) https://BioRender.com/ (accessed on 29 July 2025).CC BY · PubMed Central
Figure 5 Graphical illustration of the chicken embryo (a) and the CAM (b). The CAM comprises two different layers and a blood vessel system. Created in Biorender. Julia Nowak-Jary. (2025) https://BioRender.com/ (accessed on 29 July 2025) and Ideogram.ai. https://ideogram.ai/t/my-images (accessed on 29 July 2025).
Figure 5 Graphical illustration of the chicken embryo (a) and the CAM (b). The CAM comprises two different layers and a blood vessel system. Created in Biorender. Julia Nowak-Jary. (2025) https://BioRender.com/ (accessed on 29 July 2025) and Ideogram.ai. https://ideogram.ai/t/my-images (accessed on 29 July 2025).CC BY · PubMed Central

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Metadata

Authors
Nowak-Jary, J., & Machnicka, B.
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2025-09-03
Volume
26
Issue
17
Pages
8586
ISSN
1422-0067
DOI
10.3390/ijms26178586
PMC
PMC12428864
Cited by
25
References
7
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)

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Nowak-Jary, J., & Machnicka, B. (2025). Toxicity of Magnetic Nanoparticles in Medicine: Contributing Factors and Modern Assessment Methods. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms26178586