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

Authors Schlachter EK, Widmer HR, Bregy A, Lönnfors, Vajtai, Corazza N, Bernau, Weitzel T, Mordasini, Slotboom, Herrmann, Bogni, Hofmann H, Frenz M, Reinert M

Published 26 August 2011 Volume 2011:6 Pages 1793—1800


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Eva K Schlachter1, Hans Ruedi Widmer1, Amadé Bregy1, Tarja Lönnfors-Weitzel2, Istvan Vajtai3, Nadia Corazza3, Vianney JP Bernau6, Thilo Weitzel2, Pasquale Mordasini2, Johannes Slotboom2, Gudrun Herrmann4, Serge Bogni5, Heinrich Hofmann6, Martin Frenz5, Michael Reinert1
1Department of Neurosurgery, 2Institute for Diagnostic and Interventional Neuroradiology, 3Department of Pathology, 4Institute of Anatomy, 5Institute of Applied Physics, University of Bern, Berne, Switzerland; 6Laboratory of Powder Technology, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

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.

Keywords: superparamagnetic iron oxide nanoparticles, metabolism, distribution

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