Treatment Efficiency of Free and Nanoparticle-Loaded Mitoxantrone for Magnetic Drug Targeting in Multicellular Tumor Spheroids
by
Annkathrin Hornung 1,2, Marina Poettler 1, Ralf P. Friedrich 1, Jan Zaloga 1, Harald Unterweger 1, Stefan Lyer 1, Johannes Nowak 3, Stefan Odenbach 3, Christoph Alexiou 1 and Christina Janko 1,*
Annkathrin Hornung 1,2, Marina Poettler 1, Ralf P. Friedrich 1, Jan Zaloga 1, Harald Unterweger 1, Stefan Lyer 1, Johannes Nowak 3, Stefan Odenbach 3, Christoph Alexiou 1 and Christina Janko 1,*
1
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
2
Friedrich-Alexander-University Erlangen-Nuremberg (FAU), 91054 Erlangen, Germany
3
Chair of Magnetofluiddynamics, Measuring and Automation Technology, Technische Universität Dresden, 01062 Dresden, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Didier Astruc
Molecules 2015, 20(10), 18016-18030; https://doi.org/10.3390/molecules201018016
Received: 14 August 2015 / Revised: 14 September 2015 / Accepted: 24 September 2015 / Published: 30 September 2015
(This article belongs to the Collection Nanomedicine)
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 (SPIONMTO) are able to penetrate into tumor spheroids and thereby kill tumor cells, whereas unloaded SPION did not affect cellular viability. Since SPIONMTO 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.
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Keywords:
nanomedicine; magnetic drug targeting; superparamagnetic iron oxide nanoparticles; multicellular tumor spheroids; chemotherapy
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MDPI and ACS Style
Hornung, A.; Poettler, M.; Friedrich, R.P.; Zaloga, J.; Unterweger, H.; Lyer, S.; Nowak, J.; Odenbach, S.; Alexiou, C.; Janko, C. Treatment Efficiency of Free and Nanoparticle-Loaded Mitoxantrone for Magnetic Drug Targeting in Multicellular Tumor Spheroids. Molecules 2015, 20, 18016-18030.
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