Manganese-zinc ferrite nanoparticles were synthesized by using a hydrothermal treatment, coated with silica, and then tested as efficient cellular labels for cell tracking, using magnetic resonance imaging (MRI) in vivo. A toxicity study was performed on rat mesenchymal stem cells and C6 glioblastoma cells. Adverse effects on viability and cell proliferation were observed at the highest concentration (0.55 mM) only; cell viability was not compromised at lower concentrations. Nanoparticle internalization was confirmed by transmission electron microscopy. The particles were found in membranous vesicles inside the cytoplasm. Although the metal content (0.42 pg Fe/cell) was lower compared to commercially available iron oxide nanoparticles, labeled cells reached a comparable relaxation rate R 2, owing to higher nanoparticle relaxivity. Cells from transgenic luciferase-positive rats were used for in vivo experiments. Labeled cells were transplanted into the muscles of non-bioluminescent rats and visualized by MRI. The cells produced a distinct hypointense signal in T2- or T2*-weighted MR images in vivo. Cell viability in vivo was verified by bioluminescence.

• Keywords
• cell labeling, cell transplantation, doping, magnetic resonance imaging, nanoparticles,
• Publication type
• Journal Article MeSH

INTRODUCTION: Magnetic nanoparticles (NPs) represent a tool for use in magnetic resonance imaging (MRI)-guided thermoablation of tumors using an external high-frequency (HF) magnetic field. To avoid local overheating, perovskite NPs with a lower Curie temperature (T c) were proposed for use in thermotherapy. However, deposited power decreases when approaching the Curie temperature and consequently may not be sufficient for effective ablation. The goal of the study was to test this hypothesis. METHODS: Perovskite NPs (T c =66°C-74°C) were characterized and tested both in vitro and in vivo. In vitro, the cells suspended with NPs were exposed to a HF magnetic field together with control samples. In vivo, a NP suspension was injected into a induced tumor in rats. Distribution was checked by MRI and the rats were exposed to a HF field together with control animals. Apoptosis in the tissue was evaluated. RESULTS AND DISCUSSION: In vitro, the high concentration of suspended NPs caused an increase of the temperature in the cell sample, leading to cell death. In vivo, MRI confirmed distribution of the NPs in the tumor. The temperature in the tumor with injected NPs did not increase substantially in comparison with animals without particles during HF exposure. We proved that the deposited power from the NPs is too small and that thermoregulation of the animal is sufficient to conduct the heat away. Histology did not detect substantially higher apoptosis in NP-treated animals after ablation. CONCLUSION: Magnetic particles with low T c can be tracked in vivo by MRI and heated by a HF field. The particles are capable of inducing cell apoptosis in suspensions in vitro at high concentrations only. However, their effect in the case of extracellular deposition in vivo is questionable due to low deposited power and active thermoregulation of the tissue.

• Keywords
• MRI, high-frequency magnetic field, hyperthermia, perovskite nanoparticles, tumor ablation,
• MeSH
• Ablation Techniques instrumentation   methods   MeSH
• Hyperthermia, Induced methods   MeSH
• Contrast Media * chemistry   pharmacokinetics   MeSH
• Magnetic Resonance Imaging instrumentation   methods   MeSH
• Magnets MeSH
• Cell Line, Tumor MeSH
• Nanoparticles * chemistry   MeSH
• Silicon Dioxide chemistry   MeSH
• Oxides chemistry   MeSH
• Rats, Wistar MeSH
• Calcium Compounds chemistry   MeSH
• Suspensions MeSH
• Temperature MeSH
• Titanium chemistry   MeSH
• Xenograft Model Antitumor Assays MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Contrast Media * MeSH
• Silicon Dioxide MeSH
• Oxides MeSH
• perovskite MeSH Browser
• Calcium Compounds MeSH
• Suspensions MeSH
• Titanium MeSH