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Int. J. Mol. Sci. 2013, 14(4), 7341-7355; doi:10.3390/ijms14047341
Article

Magnetic Drug Targeting Reduces the Chemotherapeutic Burden on Circulating Leukocytes

1,2,†
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2,†,* , 1
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2
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1
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2
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1
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1
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1,‡
 and
2,‡
1 Department of Internal Medicine 3, Friedrich-Alexander-University Erlangen-Nuremberg, Ulmenweg 18, Erlangen 91054, Germany 2 Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON), University Hospital Erlangen, Waldstrasse 1, Erlangen 91054, Germany These authors contributed equally to this work. These authors contributed equally to senior authorship.
* Author to whom correspondence should be addressed.
Received: 3 December 2012 / Revised: 8 March 2013 / Accepted: 8 March 2013 / Published: 2 April 2013
(This article belongs to the Special Issue Bioactive Nanoparticles 2012)
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Abstract

Magnetic drug targeting (MDT) improves the integrity of healthy tissues and cells during treatment with cytotoxic drugs. An anticancer drug is bound to superparamagnetic iron oxide nanoparticles (SPION), injected into the vascular supply of the tumor and directed into the tumor by means of an external magnetic field. In this study, we investigated the impact of SPION, mitoxantrone (MTO) and SPIONMTO on cell viability in vitro and the nonspecific uptake of MTO into circulating leukocytes in vivo. MDT was compared with conventional chemotherapy. MTO uptake and the impact on cell viability were assessed by flow cytometry in a Jurkat cell culture. In order to analyze MTO loading of circulating leukocytes in vivo, we treated tumor-bearing rabbits with MDT and conventional chemotherapy. In vitro experiments showed a dose-dependent MTO uptake and reduction in the viability and proliferation of Jurkat cells. MTO and SPIONMTO showed similar cytotoxic activity. Non-loaded SPION did not have any effect on cell viability in the concentrations tested. Compared with systemic administration in vivo, MDT employing SPIONMTO significantly decreased the chemotherapeutic load in circulating leukocytes. We demonstrated that MDT spares the immune system in comparison with conventional chemotherapy.
Keywords: chemotherapy; iron oxide nanoparticles; mitoxantrone; magnetic drug targeting; immune system; leukocytes chemotherapy; iron oxide nanoparticles; mitoxantrone; magnetic drug targeting; immune system; leukocytes
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Janko, C.; Dürr, S.; Munoz, L.E.; Lyer, S.; Chaurio, R.; Tietze, R.; Löhneysen, S.V.; Schorn, C.; Herrmann, M.; Alexiou, C. Magnetic Drug Targeting Reduces the Chemotherapeutic Burden on Circulating Leukocytes. Int. J. Mol. Sci. 2013, 14, 7341-7355.

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