title: Treatment Efficiency of Free and Nanoparticle-Loaded Mitoxantrone for Magnetic Drug Targeting in Multicellular Tumor Spheroids.
abstract: Major problems of cancer treatment using systemic chemotherapy are severe side effects. Magnetic drug targeting (MDT) employing superparamagnetic iron oxide nanoparticles (SPION) loaded with chemotherapeutic agents may overcome this dilemma by increasing drug accumulation in the tumor and reducing toxic side effects in the healthy tissue. For translation of nanomedicine from bench to bedside, nanoparticle-mediated effects have to be studied carefully. In this study, we compare the effect of SPION, unloaded or loaded with the cytotoxic drug mitoxantrone (MTO) with the effect of free MTO, on the viability and proliferation of HT-29 cells within three-dimensional multicellular tumor spheroids. Fluorescence microscopy and flow cytometry showed that both free MTO, as well as SPION-loaded MTO (SPION(MTO)) are able to penetrate into tumor spheroids and thereby kill tumor cells, whereas unloaded SPION did not affect cellular viability. Since SPION(MTO) has herewith proven its effectivity also in complex multicellular tumor structures with its surrounding microenvironment, we conclude that it is a promising candidate for further use in magnetic drug targeting in vivo.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung Professorship, University Hospital Erlangen, Glückstraße 10a, 91054 Erlangen, Germany. annkathrin.hornung@uk-erlangen.de.|Friedrich-Alexander-University Erlangen-Nuremberg (FAU), 91054 Erlangen, Germany. annkathrin.hornung@uk-erlangen.de.
authors.forename: Annkathrin
authors.initials: A
authors.lastname: Hornung
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung Professorship, University Hospital Erlangen, Glückstraße 10a, 91054 Erlangen, Germany. marina.poettler@uk-erlangen.de.
authors.forename: Marina
authors.initials: M
authors.lastname: Poettler
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung Professorship, University Hospital Erlangen, Glückstraße 10a, 91054 Erlangen, Germany. ralf.friedrich@uk-erlangen.de.
authors.forename: Ralf P
authors.initials: RP
authors.lastname: Friedrich
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung Professorship, University Hospital Erlangen, Glückstraße 10a, 91054 Erlangen, Germany. jan.zaloga@uk-erlangen.de.
authors.forename: Jan
authors.initials: J
authors.lastname: Zaloga
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung Professorship, University Hospital Erlangen, Glückstraße 10a, 91054 Erlangen, Germany. harald.unterweger@uk-erlangen.de.
authors.forename: Harald
authors.initials: H
authors.lastname: Unterweger
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung Professorship, University Hospital Erlangen, Glückstraße 10a, 91054 Erlangen, Germany. stefan.lyer@uk-erlangen.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lyer
authors.affiliation: Chair of Magnetofluiddynamics, Measuring and Automation Technology, Technische Universität Dresden, 01062 Dresden, Germany. johannes.nowak@tu-dresden.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Nowak
authors.affiliation: Chair of Magnetofluiddynamics, Measuring and Automation Technology, Technische Universität Dresden, 01062 Dresden, Germany. stefan.odenbach@tu-dresden.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Odenbach
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung Professorship, University Hospital Erlangen, Glückstraße 10a, 91054 Erlangen, Germany. christoph.alexiou@uk-erlangen.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Alexiou
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung Professorship, University Hospital Erlangen, Glückstraße 10a, 91054 Erlangen, Germany. christina.janko@uk-erlangen.de.
authors.forename: Christina
authors.initials: C
authors.lastname: Janko
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D058185:Magnetite Nanoparticles; D008942:Mitoxantrone / Q000008:administration & dosage / Q000494:pharmacology*; D018874:Spheroids, Cellular; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D058185:Magnetite Nanoparticles; D008942:Mitoxantrone
keywords: chemotherapy; magnetic drug targeting; multicellular tumor spheroids; nanomedicine; superparamagnetic iron oxide nanoparticles