Effect of Citrate- and Gold-Stabilized Superparamagnetic Iron Oxide Nanoparticles on Head and Neck Tumor Cell Lines during Combination Therapy with Ionizing Radiation

Christoph Schreiber; Tim Franzen; Laura Hildebrand; René Stein; Bernhard Friedrich; Rainer Tietze; Rainer Fietkau; Luitpold V Distel

doi:10.3390/bioengineering9120806

Effect of Citrate- and Gold-Stabilized Superparamagnetic Iron Oxide Nanoparticles on Head and Neck Tumor Cell Lines during Combination Therapy with Ionizing Radiation

Bioengineering (Basel). 2022 Dec 15;9(12):806. doi: 10.3390/bioengineering9120806.

Authors

Christoph Schreiber^{1

2}, Tim Franzen^{1

2}, Laura Hildebrand^{1

2}, René Stein³, Bernhard Friedrich³, Rainer Tietze³, Rainer Fietkau^{1

2}, Luitpold V Distel^{1

2}

Affiliations

¹ Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany.
² Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, Germany.
³ ENT-Department, Else Kröner-Fresenius-Stiftung Professorship, Section for Experimental Oncology and Nanomedicine (SEON), University Hospital Erlangen, 91054 Erlangen, Germany.

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. They are associated with alcohol and tobacco consumption, as well as infection with human papillomaviruses (HPV). Therapeutic options include radiochemotherapy, surgery or chemotherapy. Nanoparticles are becoming more and more important in medicine. They can be used diagnostically, but also therapeutically. In order to provide therapeutic alternatives in the treatment of HNSCC, the effect of citrate-coated superparamagnetic iron oxide nanoparticles (Citrate-SPIONs) and gold-coated superparamagnetic iron oxide nanoparticles (Au-SPIONs) in combination with ionizing irradiation (IR) on two HPV positive and two HPV negative HNSCC and healthy fibroblasts and keratinocytes cell lines were tested. Effects on apoptosis and necrosis were analyzed by using flow cytometry. Cell survival studies were performed with a colony formation assay. To better understand where the SPIONs interact, light microscopy images and immunofluorescence studies were performed. The HNSCC and healthy cell lines showed different responses to the investigated SPIONs. The cytotoxic effects of SPIONs, in combination with IR, are dependent on the type of SPIONs, the dose administered and the cell type treated. They are independent of HPV status. Reasons for the different cytotoxic effect are probably the different compositions of the SPIONs and the related different interaction of the SPIONs intracellularly and paramembranously, which lead to different strong formations of double strand breaks.

Keywords: citrate; gold; head and neck cancer cell lines; interactions; ionizing radiation; nanoparticles; superparamagnetic iron oxide nanoparticles.

Grants and funding

We acknowledge financial support by Deutsche Forschungsgemeinschaft and Friedrich-Alexander-Universität Erlangen-Nürnberg within the funding programme “Open Access Publication Funding”.