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Magnetic Drug Targeting Reduces the Chemotherapeutic Burden on Circulating Leukocytes
Department of Internal Medicine 3, Friedrich-Alexander-University Erlangen-Nuremberg, Ulmenweg 18, Erlangen 91054, Germany
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; in revised form: 8 March 2013 / Accepted: 8 March 2013 / Published: 2 April 2013
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
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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.
Janko C, Dürr S, Munoz LE, Lyer S, Chaurio R, Tietze R, Löhneysen SV, Schorn C, Herrmann M, Alexiou C. Magnetic Drug Targeting Reduces the Chemotherapeutic Burden on Circulating Leukocytes. International Journal of Molecular Sciences. 2013; 14(4):7341-7355.
Janko, Christina; Dürr, Stephan; Munoz, Luis E.; Lyer, Stefan; Chaurio, Ricardo; Tietze, Rainer; Löhneysen, Sarah V.; Schorn, Christine; Herrmann, Martin; Alexiou, Christoph. 2013. "Magnetic Drug Targeting Reduces the Chemotherapeutic Burden on Circulating Leukocytes." Int. J. Mol. Sci. 14, no. 4: 7341-7355.