Biological impact of superparamagnetic iron oxide nanoparticles for magnetic particle imaging of head and neck cancer cells.
BACKGROUND
As a tomographic imaging technology, magnetic particle imaging (MPI) allows high spatial resolution and sensitivity, and the possibility to create real-time images by determining the spatial distribution of magnetic particles. To ensure a prospective biosafe application of UL-D (University of Luebeck-Dextran coated superparamagnetic nanoparticles), we evaluated the biocompatibility of superparamagnetic iron oxide nanoparticles (SPIONs), their impact on biological properties, and their cellular uptake using head and neck squamous cancer cells (HNSCCs).


METHODS
SPIONs that met specific MPI requirements were synthesized as tracers. Labeling and uptake efficiency were analyzed by hematoxylin and eosin staining and magnetic particle spectrometry. Flow cytometry, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays, and real-time cell analyzer assays were used to investigate apoptosis, proliferation, and the cytokine response of SPION-labeled cells. The production of reactive oxygen species (ROS) was determined using a fluorescent dye. Experimental results were compared to the contrast agent Resovist(®), a standard agent used in MPI.


RESULTS
UL-D nanoparticles and Resovist particles were taken up in vitro by HNSCCs via unspecific phagocytosis followed by cytosolic accumulation. To evaluate toxicity, flow cytometry analysis was performed; results showed that dose- and time-dependent administration of Resovist induced apoptosis whereas cell viability of UL-D-labeled cells was not altered. We observed decreased cell proliferation in response to increased SPION concentrations. An intracellular production of ROS could not be detected, suggesting that the particles did not cause oxidative stress. Tumor necrosis factor alpha (TNF-α) and interleukins IL-6, IL-8, and IL-1β were measured to distinguish inflammatory responses. Only the primary tumor cell line labeled with >0.5 mM Resovist showed a significant increase in IL-1β secretion.


CONCLUSIONS
Our data suggest that UL-D SPIONs are a promising tracer material for use in innovative tumor cell analysis in MPI.
Department of Otorhinolaryngology, University Hospital of Schleswig-Holstein, Luebeck, Germany.
Antje
A
Lindemann
Institute of Medical Engineering, University of Luebeck, Luebeck, Germany.
Kerstin
K
Lüdtke-Buzug
Department of Otorhinolaryngology, University Hospital of Schleswig-Holstein, Luebeck, Germany.
Bianca M
BM
Fräderich
Institute of Medical Engineering, University of Luebeck, Luebeck, Germany.
Ksenija
K
Gräfe
Department of Otorhinolaryngology, University Hospital of Schleswig-Holstein, Luebeck, Germany.
Ralph
R
Pries
Department of Otorhinolaryngology, University Hospital of Schleswig-Holstein, Luebeck, Germany.
Barbara
B
Wollenberg
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D003952:Diagnostic Imaging / Q000379:methods*; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006801:Humans; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism
D016207:Cytokines; D058185:Magnetite Nanoparticles; D017382:Reactive Oxygen Species
HNSCCs; biomedical imaging; cell labeling; cytotoxicity; iron oxide nanoparticles