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Selection of potential iron oxide nanoparticles for breast cancer treatment based on in vitro cytotoxicity and cellular uptake

Authors Poller JM, Zaloga J, Schreiber E, Unterweger H, Janko C, Radon P, Eberbeck D, Trahms L, Alexiou C, Friedrich RP

Received 13 January 2017

Accepted for publication 1 March 2017

Published 19 April 2017 Volume 2017:12 Pages 3207—3220

DOI https://doi.org/10.2147/IJN.S132369

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Thomas Webster


Johanna M Poller,1,2 Jan Zaloga,1 Eveline Schreiber,1 Harald Unterweger,1 Christina Janko,1 Patricia Radon,3 Dietmar Eberbeck,3 Lutz Trahms,3 Christoph Alexiou,1 Ralf P Friedrich1

1Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology & Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung Professorship, Universitätsklinikum Erlangen, Erlangen, 2Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 3Physikalisch-Technische Bundesanstalt Braunschweig und Berlin, Berlin, Germany

Abstract: Superparamagnetic iron oxide nanoparticles (SPIONs) are promising tools for the treatment of different diseases. Their magnetic properties enable therapies involving magnetic drug targeting (MDT), hyperthermia or imaging. Depending on the intended treatment, specific characteristics of SPIONs are required. While particles used for imaging should circulate for extended periods of time in the vascular system, SPIONs intended for MDT or hyperthermia should be accumulated in the target area to come into close proximity of, or to be incorporated into, specific tumor cells. In this study, we determined the impact of several accurately characterized SPION types varying in size, zeta potential and surface coating on various human breast cancer cell lines and endothelial cells to identify the most suitable particle for future breast cancer therapy. We analyzed cellular SPION uptake, magnetic properties, cell proliferation and toxicity using atomic emission spectroscopy, magnetic susceptometry, flow cytometry and microscopy. The results demonstrated that treatment with dextran-coated SPIONs (SPIONDex) and lauric acid-coated SPIONs (SPIONLA) with an additional protein corona formed by human serum albumin (SPIONLA-HSA) resulted in very moderate particle uptake and low cytotoxicity, whereas SPIONLA had in part much stronger effects on cellular uptake and cellular toxicity. In summary, our data show significant dose-dependent and particle type-related response differences between various breast cancer and endothelial cells, indicating the utility of these particle types for distinct medical applications.

Keywords: breast cancer, superparamagnetic iron oxide nanoparticles, cellular SPION uptake, toxicity, flow cytometry

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