Toxicity and bioresorption of magnetite and manganese-zinc ferrite nanoparticles with oleic acid-based and amino-silica coatings

Authors

DOI:

https://doi.org/10.18413/rrpharmacology.12.1165%20%20

Abstract

Introduction: The prospects for using magnetic hyperthermia in cancer therapy are largely determined by the properties of the magnetic nanoparticles (MNPs), including heating efficiency, biosafety, and bioresorption capacity. In this study, we performed a comparative in vivo assessment of the toxicity and bioresorption of Fe3O4- and Zn0.2Mn0.8Fe2O4-based MNPs stabilized with oleic acid/sodium oleate (OA) or amino-functionalized silicon dioxide (SiO2–NH2).

Materials and Methods: Four types of MNPs were synthesized: Fe3O4@OA, Zn0.2Mn0.8Fe2O4@OA, Fe3O4@SiO2–NH2 and Zn0.2Mn0.8Fe2O4@SiO2–NH2. The particles were characterized using DLS, TEM and vibrating sample magnetometry. Acute toxicity was evaluated in BALB/c mice after a single intraperitoneal or intramuscular administration. Biosafety and bioresorption after intramuscular administration were assessed on days 2, 14, and 90, using hematological and biochemical blood tests, histological examination, sample magnetization, and total iron content in tissues.

Results and Discussion: After intraperitoneal administration, the LD50 values were 904 mg/kg for Fe3O4@OA, 1145 mg/kg for Zn0.2Mn0.8Fe2O4@OA, and 2955 mg/kg for Zn0.2Mn0.8Fe2O4@SiO2–NH2, whereas the LD50 for Fe3O4@SiO2–NH2 was not reached. After intramuscular administration at a dose of 1020 mg/kg, neither deaths nor pronounced systemic toxicity was observed. By day 90, MNPs with an oleic acid/sodium oleate-based coating showed a decrease in magnetic signal and total iron content at the injection site, whereas SiO2–NH2-coated nanoparticles remained in muscle tissue.

Conclusion: The study showed that the chemical nature of the coating is one of the main factors determining the toxicity and bioresorption of Fe3O4 and Zn0.2Mn0.8Fe2O4 MNPs. Particles with a SiO2–NH2 coating were characterized by lower acute toxicity after intraperitoneal administration compared with MNPs coated with oleic acid/sodium oleate. After intramuscular administration at a dose of 1020 mg/kg, neither mortality nor pronounced signs of systemic toxicity were detected for any type of MNPs. It was also shown that the coating type affects the possibility and rate of bioresorption: after intramuscular administration at a dose of 256 mg/kg, MNPs with a SiO2–NH2 coating remained at the injection site for 90 days, whereas the oleic acid/sodium oleate-based coating promoted bioresorption.

 

Graphical Abstract

Keywords:

acute toxicity, bioresorption, magnetic hyperthermia, magnetic nanoparticles, oleic acid

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Author Contribution

Denis E. Yakobson, National Research Ogarev Mordovia State University

Junior Researcher, Educational and Research Laboratory of Preclinical and Clinical Trials of Targeted Drug Forms, Federal Center for Biotechnology and Medicine Advancement, National Research Ogarev Mordovia State University, Saransk, Russia; e-mail: ykbsn@mail.ru; ORCID ID: https://orcid.org/0000-0002-7675-0823. Study planning and general supervision, experimental design, conducting the experiment, literature analysis, manuscript writing, and translation of the manuscript in English.

Vasilisa I. Kulikova, National Research Ogarev Mordovia State University

Junior Researcher, Laboratory of Drug Toxicology and Specific Activity with Vivarium, Federal Center for Biotechnology and Medicine Advancement, National Research Ogarev Mordovia State University, Saransk, Russia; e-mail: 98@mail.ru; ORCID ID:https://orcid.org/0000-0002-5248-0136. Experimental design development, conducting the experiment, and literature analysis.

Vladislav S. Bobrov, National Research Ogarev Mordovia State University

Research Engineer, Laboratory of Drug Toxicology and Specific Activity with Vivarium, Federal Center for Biotechnology and Medicine Advancement, National Research Ogarev Mordovia State University, Saransk, Russia; e-mail: vlad_bobrov_02@list.ru; ORCID ID:https://orcid.org/0009-0001-0478-3634. Conducting the experiment, analysis of clinical manifestations, and statistical data analysis.

Anna A. Gadeeva, National Research Ogarev Mordovia State University

Junior Researcher, Laboratory of Drug Toxicology and Specific Activity with Vivarium, Federal Center for Biotechnology and Medicine Advancement, National Research Ogarev Mordovia State University, Saransk, Russia; e-mail: annaggga@yandex.ru; ORCID ID:https://orcid.org/0009-0005-9549-8976. Conducting the experiment, analysis of clinical manifestations, and statistical data analysis.

Mikhail N. Zharkov, National Research Ogarev Mordovia State University

Head of the Laboratory of Pharmacokinetics and Targeted Pharmacotherapy, Federal Center for Biotechnology and Medicine Advancement, National Research Ogarev Mordovia State University, Saransk, Russia; e-mail: zharkov.92@mail.ru; ORCID ID: https://orcid.org/0000-0002-8272-1973. Experimental design development, literature analysis, and manuscript writing.

Mikhail V. Zhuravlev, National Research Ogarev Mordovia State University

Undergraduate student, Medical Institute, National Research Ogarev Mordovia State University, Saransk, Russia; e-mail: mihailzhyravlev@gmail.com; ORCID ID: https://orcid.org/0009-0000-3931-3803. Conducting the experiment, analysis of clinical manifestations, and statistical data analysis.

Razmik G. Akopyan, National Research Ogarev Mordovia State University

Undergraduate student of the Institute of High Technologies and New Materials, National Research Ogarev Mordovia State University, Saransk, Russia; e-mail: ramzik_aga@mail.ru; ORCID ID: https://orcid.org/0009-0003-3612-8225. Conducting the experiment, analysis of clinical manifestations, and statistical data analysis.

Anastasia S. Poletaeva, National Research Ogarev Mordovia State University

Undergraduate student, Medical Institute, National Research Ogarev Mordovia State University, Saransk, Russia; e-mail: poletaeva8@gmail.com; ORCID ID: https://orcid.org/0009-0002-6359-9260. Conducting the experiment, analysis of clinical manifestations, and statistical data analysis.

Mikhail V. Gerasimov, National Research Ogarev Mordovia State University

Senior Researcher, Institute of High Technologies and New Materials, National Research Ogarev Mordovia State University, Saaransk, Russia; e-mail: mv12@gmail.com; ORCID ID: https://orcid.org/0000-0002-7163-4612. Conducting the experiment, experimental design development, and statistical data analysis.

Oleg A. Kulikov, National Research Ogarev Mordovia State University

Doctor Habil. of Medical Sciences, Associate Professor, Head of the Laboratory of Drug Toxicology and Specific Activity with Vivarium, Federal Center for Biotechnology and Medicine Advancement, National Research Ogarev Mordovia State University, Saransk, Russia; e-mail: oleg-kulikov-84@mail.ru; ORCID ID: https://orcid.org/0000-0003-4411-677X. Study planning and general supervision, experimental design development, literature analysis, and manuscript writing.

Nikolay A. Pyataev, National Research Ogarev Mordovia State University

Doctor Habil. of Medical Sciences, Associate Professor, Head of the Federal Center for Biotechnology and Medicine Advancement, National Research Ogarev Mordovia State University, Saransk, Russia; e-mail: pyataevna@mail.ru; ORCID ID: https://orcid.org/0000-0002-9688-7640. Study planning and general supervision, experimental design development, literature analysis, and manuscript writing.

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10-09-2026

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Yakobson DE, Kulikova VI, Bobrov VS, Gadeeva AA, Zharkov MN, Zhuravlev MV, Akopyan RG, Poletaeva AS, Gerasimov MV, Kulikov OA, Pyataev NA (2026) Toxicity and bioresorption of magnetite and manganese-zinc ferrite nanoparticles with oleic acid-based and amino-silica coatings. Research Results in Pharmacology 12(3): 1–17. https://doi.org/10.18413/rrpharmacology.12.1165

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Vol. 12 No. 3 (2026)

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Experimental Pharmacology

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Copyright (c) 2026 Yakobson DE, Kulikova VI, Bobrov VS, Gadeeva AA, Zharkov MN, Zhuravlev MV, Akopyan RG, Poletaeva AS, Gerasimov MV, Kulikov OA, Pyataev NA

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