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[Toxicity of magnetite-dextran particles: morphological study]
E E Okon1, D Pulikan, A E Pereverzev
1Institute of Cytology, Russian Academy of Sciences, St. Petersburg. callpath@link.cytspb.rssi.ru
Abstract:
Females of OFI mice were given single repeated intravenous injections of magnetite-dextran nanoparticles (MD3), the total partical diameter being 49 nm, with the magnetic core diameter equal to 10-15 nm. MD3 is a superparamagnetic preparation commonly used for magnetic resonance imaging (MRI). The liver, spleen, heart, kidney, and lung microstructures of these mice were determined after MD3 administration. Both dose- and time-dependent changes in the examined organs were compared after single and repeated MD3 doses. MD3 induces an increse in ferritine and iron levels in all the organs, the appearance of small aggregates of lymphoid cells in the liver, the appearance of iron-containing cell formations in hepatic sinusoids, presumably composed of the Kupffer cells and portal macrophages, splenomegaly, and hemostasis of spleen blood vessels. The pronounced morphological alterations have been revealed primarily in the liver and spleen after a single administration of high MD3 doses and after repeated MD3 injections. The results of The present investigation seem to narrow somewhat the safety limits of superparamagnetic iron oxide particles. Nevertheless, the degree of morphological changes in the liver and spleen in our experiments appeared to be rather low even after a single MD3 dose that exceeds approximately by 200 times a dose necessary for diagnostics in MRI.
Insights
Repeated intravenous injections of magnetite-dextran nanoparticles (MD3) in mice caused dose- and time-dependent changes in the liver and spleen. While iron levels increased, morphological alterations were minimal, suggesting a relatively safe profile for MRI contrast agents.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Toxicology
Background:
- Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used as contrast agents in magnetic resonance imaging (MRI).
- Magnetite-dextran nanoparticles (MD3) are a specific type of SPION utilized for diagnostic purposes.
- Understanding the in vivo biodistribution and potential toxicity of SPIONs is crucial for clinical safety.
Purpose of the Study:
- To evaluate the dose- and time-dependent effects of magnetite-dextran nanoparticles (MD3) on the microstructure of major organs in OFI mice.
- To assess the safety profile of MD3 following single and repeated intravenous administrations.
- To determine the morphological changes induced by MD3 in the liver, spleen, heart, kidney, and lung.
Main Methods:
- Female OFI mice received single or repeated intravenous injections of magnetite-dextran nanoparticles (MD3) with a total particle diameter of 49 nm and a magnetic core diameter of 10-15 nm.
- Histopathological examination of liver, spleen, heart, kidney, and lung tissues was performed at various time points post-administration.
- Changes in ferritin and iron levels were quantified in the examined organs.
Main Results:
- MD3 administration led to increased ferritin and iron levels in all examined organs.
- Observed morphological changes included lymphoid cell aggregates and iron-containing Kupffer cells/macrophages in the liver, and splenomegaly with vascular hemostasis in the spleen.
- Pronounced alterations were primarily noted in the liver and spleen, particularly after high single doses and repeated injections.
Conclusions:
- Magnetite-dextran nanoparticles (MD3) induce dose- and time-dependent morphological and biochemical changes in mouse organs, primarily the liver and spleen.
- Despite observed changes, the degree of morphological alterations remained relatively low, even at doses significantly exceeding diagnostic levels.
- These findings suggest that while SPIONs like MD3 have a generally low toxicity profile, their safety limits may require further refinement based on administration protocols.