Biological impact of superparamagnetic iron oxide nanoparticles for magnetic particle imaging of head and neck cancer cells

Abstract

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. Conclusion Our data suggest that UL-D SPIONs are a promising tracer material for use in innovative tumor cell analysis in MPI.

Iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model

“…14 In order to examine if the cytokine response in our study was accompanied by ROS production, we measured intracellular ROS in the whole blood samples after 2 and 4 h. The IONPs did not significantly increase ROS compared with the control samples, which is in agreement with previous findings. 30,31 However, our results are in contrast to other studies that show IONP-induced ROS production. [32][33][34][35] Possible explanations for the discrepancies include one or more of the following factors: different types and sizes of IONPs used; different surface properties (eg, surface coatings) of the IONPs that affect the degradation potential and thus the exposure to the naked iron oxide core and the liberation of iron ions that might induce ROS; 32 different cell types used; higher IONP concentration; different (mostly longer) incubation times after which ROS production was measured and/or different methods for assessing intracellular ROS.…”

Towards Picogram Detection of Superparamagnetic Iron-Oxide Particles Using a Gradiometric Receive Coil

“…Cell labeling and cell tracking are further very important applications for MPI 13 that potentially allow for direct imaging of cell movements in vivo. It has been shown that MPI can track the long-term fate of in vivo neural cell implants with high image contrast 14 .…”

Tracking stem cells with superparamagnetic iron oxide nanoparticles: perspectives and considerations

“…38 Both the chemical composition and the nanostructure of the material are responsible for the characteristics exploited for several applications in biological sciences, such as superparamagnetism. 39,40 Biocompatible SPIONs, such as magnetite, have been widely used for in vivo biomedical applications. Their slower renal clearance and higher relaxation values compared with the gadolinium-based contrast agents make them more attractive for imaging purposes.…”