Cellular effects of paclitaxel-loaded iron oxide nanoparticles on breast cancer using different 2D and 3D cell culture models

Stephan Lugert,1,2 Harald Unterweger,1 Marina Mühlberger,1 Christina Janko,1 Sebastian Draack,3 Frank Ludwig,3 Dietmar Eberbeck,4 Christoph Alexiou,1 Ralf P Friedrich1 1Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, Universitätsklinikum Erlangen, Erlangen, Germany; 2Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany; 3Institut für Elektrische Messtechnik und Grundlagen der Elektrotechnik, TU Braunschweig, Braunschweig, Germany; 4Physikalisch-Technische Bundesanstalt Braunschweig und Berlin, Berlin, Germany Background: Magnetic drug targeting (MDT) is an effective alternative for common drug applications, which reduces the systemic drug load and maximizes the effect of, eg, chemotherapeutics at the site of interest. After the conjugation of a magnetic carrier to a chemotherapeutic agent, the intra-arterial injection into a tumor-afferent artery in the presence of an external magnetic field ensures the accumulation of the drug within the tumor tissue.Materials and methods: In this study, we used superparamagnetic iron oxide nanoparticles (SPIONs) coated with lauric acid and human serum albumin as carriers for paclitaxel (SPIONLA-HSA-Ptx). To investigate whether this particle system is suitable for a potential treatment of cancer, we investigated its physicochemical properties by dynamic light scattering, ζ potential measurements, isoelectric point titration, infrared spectroscopy, drug release quantification, and magnetic susceptibility measurements. The cytotoxic effects were evaluated using extensive toxicological methods using flow cytometry, IncuCyte® live-cell imaging, and growth experiments on different human breast cancer cell lines in two- and three-dimensional cell cultures.Conclusion: The data showed that next to their high magnetization capability, SPIONLA-HSA-Ptx have similar cytostatic effects on human breast cancer cells as pure paclitaxel, suggesting their usage for future MDT-based cancer therapy. Keywords: superparamagnetic iron oxide nanoparticles, SPIONs, three-dimensional cell culture, toxicity, flow cytometry, magnetic drug targeting&nbsp