The biochemical and histopathological changes induced by the exposure to iron oxide nanoparticles coated with phospholipid-based polymeric micelles (IONPs-PM) in CD-1 mice lungs were analyzed. After 2, 3, 7 and 14 days following the intravenous injection of IONPs-PM (5 and 15 mg Fe/kg bw), lactate dehydrogenase (LDH) activity, oxidative stress parameters and the expression of Bax, Bcl-2, caspase-3 and TNF-α were evaluated in lung tissue. An increase of catalase (CAT) and glutathione reductase (GR) activities on the second day followed by a decrease on the seventh day, as well as a decline of lactate dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity on the third and seventh day were observed in treated groups vs. controls. However, all these enzymatic activities almost fully recovered on the 14th day. The reduced glutathione (GSH) and protein thiols levels decreased significantly in nanoparticles-treated groups and remained diminished during the entire experimental period; by contrast malondialdehyde (MDA) and protein carbonyls increased between the 3rd and 14th day of treatment vs. control. Relevant histopathological modifications were highlighted using Hematoxylin and Eosin (H&E) staining. In addition, major changes in the expression of apoptosis markers were observed in the first week, more pronounced for the higher dose. The injected IONPs-PM generated a dose-dependent decrease of the mouse lung capacity, which counteracted oxidative stress, thus creating circumstances for morphopathological lesions and oxidation processes.

Magnetic nanoparticles are intensively studied for magnetic resonance imaging (MRI) as contrast agents but yet there remained some gaps regarding their toxicity potential and clinical implications of their biodistribution in organs. This study presents the effects induced by magnetite nanoparticles encapsulated in polymeric micelles (MNP-DSPE-PEG) on biochemical markers, metabolic functions, and MRI signal in CD1 mice liver. Three groups of animals, one control and the other ones injected with a suspension of five, respectively, 15 mg Fe/kg bw nanoparticles, were monitored up to 14 days. The results indicated the presence of MNP-DSPE-PEG in the liver in the first two days of the experiment. The most significant biochemical changes also occurred in the first 3 days after exposure when the most severe histological changes were observed. The change of the MRI signal intensity on the T2-weighted images and increased transverse relaxation rates R2 in the liver were observed after the first minutes from the nanoparticle administration. The study shows that the alterations of biomarkers level resulting from exposure to MNP-DSPE-PEG are restored in time in mice liver. This was associated with a significant contrast on T2-weighted images and made us conclude that these nanoparticles might be potential candidates for use as a contrast agent in liver medical imaging.

The renal toxicity induced by the intravenously injected iron oxide nanoparticles (IONPs) encapsulated in phospholipid-based polymeric micelles was studied in CD1 mice for 2 weeks. Two doses of 5 and 15 mg of Fe/kg bodyweight of NPs or saline solution (control) were tested, and the levels of antioxidant enzyme activities, oxidative stress parameters, and the expressions of kidney fibrosis biomarkers were analyzed. The enzymatic activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase, and glucose-6-phosphate dehydrogenase in the kidney were significantly decreased compared to the control in the first 3 days followed by a recovery up to 14 days. Concomitantly, a significant increase in lipid peroxidation (malondialdehyde) levels and a decrease in protein thiol groups were recorded. Moreover, increases in the expressions of T cell immunoglobulin and mucin domain 1 (TIM-1) and transforming growth factor-β (TGF-β) were observed in mouse tissue samples in the first week, which were more pronounced for the higher dose. The results suggested the role of oxidative stress as a mechanism for induced toxicity in mice kidneys after the IV administration of IONPs encapsulated in phospholipid-based polymeric micelles but also the capacity of the kidneys’ defense systems to revert efficiently the biochemical modifications that were moderate and for short duration.