title: Magnetic drug targeting reduces the chemotherapeutic burden on circulating leukocytes.
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.
authors.affiliation: Department of Internal Medicine 3, Friedrich-Alexander-University Erlangen-Nuremberg, Ulmenweg 18, Erlangen 91054, Germany. stephan.duerr@uk-erlangen.de.
authors.forename: Christina
authors.initials: C
authors.lastname: Janko
authors.forename: Stephan
authors.initials: S
authors.lastname: Dürr
authors.forename: Luis E
authors.initials: LE
authors.lastname: Munoz
authors.forename: Stefan
authors.initials: S
authors.lastname: Lyer
authors.forename: Ricardo
authors.initials: R
authors.lastname: Chaurio
authors.forename: Rainer
authors.initials: R
authors.lastname: Tietze
authors.forename: Sarah von
authors.initials: Sv
authors.lastname: Löhneysen
authors.forename: Christine
authors.initials: C
authors.lastname: Schorn
authors.forename: Martin
authors.initials: M
authors.lastname: Herrmann
authors.forename: Christoph
authors.initials: C
authors.lastname: Alexiou
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D003603:Cytotoxins / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D019169:Jurkat Cells; D007962:Leukocytes / Q000378:metabolism* / Q000473:pathology; D060526:Magnetic Fields; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011817:Rabbits
chemical_list: D003603:Cytotoxins; D058185:Magnetite Nanoparticles
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