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Glioblastoma Cell Type-Specific Loading with Iron Oxide Magnetic Nanoparticles

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Abstract

Magnetic nanoparticles (MNPs) could support the traditional brain cancer (e.g., glioblastoma) therapy; however, the efficient cell loading remains a crucial point. We aimed to relate the impact of the in vitro setup conditions to the long-term MNP loading of different glioblastoma cell lines. For this reason, three human glioblastoma and one astrocyte primary cell cultures were incubated with two different MNP types and various concentrations for 1–3 days. The resulting cellular iron load and cytotoxicity was determined. We found that the time dependence of the cell loading was governed by a variable cell growth behavior in vitro, whereas the impact of the MNP concentration was mostly MNP type-dependent. The growth as well as the membrane integrity of the cancer cells was not remarkably affected, but in astrocytes, although the metabolic activity was altered in all cell types. Consequently, we stated that the cell behavior and a comprehensive in vitro setup are key challenges for a proper design of MNPs and their medical application.

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Acknowledgments

Dr. Ladislau Vékás from the Laboratory of Magnetic Fluids (Timisoara, Romania) kindly provided the MA used in this study and supported the study by discussions about the properties of MA. The authors want to thank Svenja Zapf for her assistance in cell culture and Heike Helmholz for the critical revision of the manuscript.

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Authors and Affiliations

  1. Helmholtz-Zentrum Geesthacht GmbH, Zentrum für Material- und Küstenforschung - Division for Metallic Biomaterials, Max-Planck-Straße 1, 21502, Geesthacht, Germany

    Dorothee Scharfenberg, Bérengère Luthringer & Regine Willumeit-Römer

  2. Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Neurochirurgie, Labor für Hirntumorbiologie, Martinistraße 52, 20446, Hamburg, Germany

    Katrin Lamszus

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  1. Dorothee Scharfenberg
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Correspondence to Bérengère Luthringer.

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This work was funded by the Technology Transfer Fund of Helmholtz-Zentrum Geesthacht GmbH, which has no involvement in the study.

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ESM 1

Suppl. Fig. 1 MNP loading of glioblastoma cell types and astrocytes. The means + standard deviations of MNP loading with 5, 25 or 50 μg/mL MA (A) or FS (B) for 1, 2 or 3 d, n = 6; *p < 0.05 compared with control, lines between the conditions, two-way ANOVA (Holm-Sidak post-hoc analysis). Suppl. Fig. 2 Cell counts after MNP loading. The means ± standard deviations of MNP loadings of glioblastom cell type and astrocytes, n = 6; #p < 0.05 compared with control, lines between the conditions, two-way ANOVA (Holm-Sidak post-hoc analysis). Suppl. Fig. 3 Time dependency of cell counts after MN. The means ± standard deviations of cell number in percent of control for all concentrations after 1, 2 or 3 d, n = 6. Suppl. Fig. 4 Correlation between Fe/cell and cell numbe sample was compared with the control mean ± standard deviation. Iron loads of samples with lower (loss), higher (gain) or similar (neutral) cell numbers were compared by ANOVA, horizontal lines indicate p < 0.05 Suppl. Fig. 5 Membrane integrity after MNP loading. The means ± standard deviations of the membrane integrity for glioblastoma cell types and astrocytes (Astro) for 5, 25 and 50 μg/mL and 1-3 d of incubation, n = 6, the lines between samples p < 0.05, two-way ANOVA (Holm-Sidak post post-hoc analysis). Suppl. Fig. 6 Metabolic activity after MNP loading. The means ± standard deviations of the metabolic activity for glioblastoma cells and astrocytes (Astro) for 5, 25 and 50 μg/mL and 1-3 d of incubation, n = 8, # p < 0.05 compared with control and lines between samples, two-way ANOVA (Holm Holm-Sidak post-hoc analysis). (PDF 2586 kb)

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Scharfenberg, D., Luthringer, B., Lamszus, K. et al. Glioblastoma Cell Type-Specific Loading with Iron Oxide Magnetic Nanoparticles. BioNanoSci. 6, 297–307 (2016). https://doi.org/10.1007/s12668-016-0363-1

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