Preliminary Study of Injury From Heating Systemically Delivered, Nontargeted Dextran–Superparamagnetic Iron Oxide Nanoparticles in Mice

Abstract

Aim: To assess the potential for injury to normal tissues in mice due to heating systemically delivered magnetic nanoparticles in an alternating magnetic field (AMF). Materials & methods: Twenty three male nude mice received intravenous injections of dextran–superparamagnetic iron oxide nanoparticles on days 1–3. On day 6, they were exposed to AMF. On day 7, blood, liver and spleen were harvested and analyzed. Results: Iron deposits were detected in the liver and spleen. Mice that had received a high-particle dose and a high AMF experienced increased mortality, elevated liver enzymes and significant liver and spleen necrosis. Mice treated with low-dose superparamagnetic iron oxide nanoparticles and a low AMF survived, but had elevated enzyme levels and local necrosis in the spleen. Conclusion: Magnetic nanoparticles producing only modest heat output can cause damage, and even death, when sequestered in sufficient concentrations. Dextran–superparamagnetic iron oxide nanoparticles are deposited in the liver and spleen, making these the sites of potential toxicity.

Original submitted 16 August 2011; Revised submitted 21 March 2012; Published online 26 July 2012

Keywords::

• hyperthermia
• liver
• magnetic nanoparticle
• SPIO
• spleen
• toxicity

Financial & competing interests disclosure

This research was supported by an award from the Prostate Cancer Foundation (CA, USA) and Safeway STAR Program (CA, USA). ICP-MS analysis was supported, in part, by the Maryland Cigarette Restitution Fund Program at the Johns Hopkins Bloomberg School of Public Health and the NIEHS Center P30 E00319. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Acknowledgements

The authors wish to thank G Holzhüter of the University of Rostock, Germany for transmission electron microscopy imaging and characterization, and acknowledge assistance from M Jones in the preparation of this manuscript.

Additional information

Funding

This research was supported by an award from the Prostate Cancer Foundation (CA, USA) and Safeway STAR Program (CA, USA). ICP-MS analysis was supported, in part, by the Maryland Cigarette Restitution Fund Program at the Johns Hopkins Bloomberg School of Public Health and the NIEHS Center P30 E00319. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.