Metabolic pathway and distribution of superparamagnetic iron oxide nanoparticles: in vivo study

Abstract

Background: Experimental tissue fusion benefits from the selective heating of superparamagnetic iron oxide nanoparticles (SPIONs) under high frequency irradiation. However, the metabolic pathways of SPIONs for tissue fusion remain unknown. Hence, the goal of this in vivo study was to analyze the distribution of SPIONs in different organs by means of magnetic resonance imaging (MRI) and histological analysis after a SPION-containing patch implantation. Methods: SPION-containing patches were implanted in rats. Three animal groups were studied histologically over six months. Degradation assessment of the SPION-albumin patch was performed in vivo using MRI for iron content localization and biodistribution. Results: No SPION degradation or accumulation into the reticuloendothelial system was detected by MRI, MRI relaxometry, or histology, outside the area of the implantation patch. Concentrations from 0.01 µg/mL to 25 µg/mL were found to be hyperintense in T1-like gradient echo sequences. The best differentiation of concentrations was found in T2 relaxometry, susceptibility-sensitive gradient echo sequences, and in high repetition time T2 images. Qualitative and semiquantitative visualization of small concentrations and accumulation of SPIONs by MRI are feasible. In histological liver samples, Kupffer cells were significantly correlated with postimplantation time, but no differences were observed between sham-treated and induction/no induction groups. Transmission electron microscopy showed local uptake of SPIONs in macrophages and cells of the reticuloendothelial system. Apoptosis staining using caspase showed no increased toxicity compared with sham-treated tissue. Implanted SPION patches were relatively inert with slow, progressive local degradation over the six-month period. No distant structural alterations in the studied tissue could be observed. Conclusion: Systemic bioavailability may play a role in specific SPION implant toxicity and therefore the local degradation process is a further aspect to be assessed in future studies.

Bioactive nanoparticle-based formulations increase survival area of perforator flaps in a rat model

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Immunological effects of iron oxide nanoparticles and iron-based complex drug formulations: Therapeutic benefits, toxicity, mechanistic insights, and translational considerations

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Cytotoxicity evaluation of carbon-encapsulated iron nanoparticles in melanoma cells and dermal fibroblasts

“…Iron oxide nanoparticles have been found to induce oxidative stress, which manifests in activation of reactive oxygen species, followed by a pro-inflammatory response and DNA damage leading to cellular apoptosis and mutagenesis (Naqvi et al 2010; Novotna et al 2012; Zhu et al 2010). Several pharmacokinetic reports indicate that the liver of laboratory animals is the most important organ involving the bioaccumulation and clearance procedures of the iron oxide nanoparticles studied in preclinical models (Schlachter et al 2011). In general, ultra-smaller superparamagnetic iron oxide (Fe 3 O 4 ) nanoparticles, also called as USPIO (under 50 nm in diameter), were found to circulate for longer than larger USPIO particles (over 50 nm), and can be gradually taken up by the reticuloendothelial system in lymph tissue and bone marrow.…”