<p>Biodistribution, Clearance And Morphological Alterations Of Intravenously Administered Iron Oxide Nanoparticles In Male Wistar Rats</p>

Abstract

IntroductionNanoparticles are used worldwide because of their unique properties, with large-scale application in various fields, such as medicine, cosmetics and industries. In view of their widespread use, the potential adverse effects of nanoparticles have become a significant cause for concern, in terms of not only human health and safety but also the environment. The present investigation focused on establishing the bioaccumulation patterns and ultrastructural changes induced by retained iron oxide nanoparticles (IONPs) in various target organs of rats.MethodsTwenty-four male Wistar rats were randomly divided into four groups. Experimental animals were intravenously administered different doses of IONPs (7.5 mg/kg, 15 mg/kg and 30 mg/kg) once in a week for 4 weeks. Urine and feces samples were collected on a daily basis to assess nanoparticle clearance and analyzed via atomic absorption spectroscopy (AAS). At the end of the experiment, rats were euthanized and different organs, including spleen, liver, kidney, lung, heart, testis and brain, were dissected. Bioaccumulation of iron in organs and ultrastructural changes induced by IONPs were determined.ResultsThe maximal concentration of iron was detected in spleen and minimal concentration in the brain. The level of iron accumulation in organs was as follows: spleen>blood>liver>kidney>lung>heart>testis>brain. The excretion profile in urine revealed maximum excretion on the day following administration that was maintained until day 28, whereas the iron content in feces remained high during the first three days after injection. A similar pattern was observed throughout the duration of the experiment. Ultrastructural alterations were detected in spleen, kidney, lung, heart, testis, brain and liver, indicative of cellular damage induced by accumulating nanoparticles in these organs.ConclusionIntravenous administration of IONPs results in ultrastructural changes and dose-dependent bioaccumulation in different organs of rats.

Superparamagnetic Iron Oxide Particles (VSOPs) Show Genotoxic Effects but No Functional Impact on Human Adipose Tissue-Derived Stromal Cells (ASCs)

“…In addition, IONPs can be directed to specific sites in the organism due to their magnetic properties. They are used for tissue engineering [ 72 ] and the delivery of biotherapeutic agents [ 40 , 70 , 73 , 74 ]. An important diagnostic application of IONPs is the labeling of cells for cell imaging by MRI.…”

“…The extension of the scope of IONPs leads to an increasing exposure of humans to these particles [ 36 , 40 ]. Recently, Gaharwar et al investigated the biodistribution and accumulation of intravenously applied IONPs in the organs of rats.…”

“…Recently, Gaharwar et al investigated the biodistribution and accumulation of intravenously applied IONPs in the organs of rats. They showed a dose-dependent accumulation of IONPs and ultrastructural changes with tissue damage [ 40 ]. However, the application of IONPs or the labeling of cells with IONPs in cell-based therapies should not lead to a change in cell properties and functions or cause lasting damage.…”

Toxicity and Functional Impairment in Human Adipose Tissue-Derived Stromal Cells (hASCs) Following Long-Term Exposure to Very Small Iron Oxide Particles (VSOPs)

“…Iron oxide nanoparticles (IONPs) are increasingly used for various applications, e.g., for the targeted administration of drugs or genes, for cancer imaging and therapy, for hyperthermia, magnetic particle imaging (MPI) and tissue engineering [1,[4][5][6][7][9][10][11]42]. In addition, the labelling of MSCs with e.g., citrate-coated VSOPs, allows non-invasive visualization and in vivo tracking by MRI in cellular therapy [1][2][3]14].…”

Iron oxide nanoparticle-induced hematopoietic and immunological response in rats

“…1,2 Due to this unique property, IONPs hold immense potential in biomedical applications such as MRI contrast agent, targeted drug delivery, tissue engineering, tissue repair, thermal ablation therapy, noninvasive in vivo cell tracking, and magnetic transfections. [2][3][4][5] Recently IONPs, feridex (ferumoxides) and feraheme (ferumoxytol) have been approved by U.S. FDA for MRI, and iron deciency treatment respectively. 2 Additionally, there are other clinical trials (NCT01411904, NCT01995799, NCT01895829 etc.…”