[Magnetically based enhancement of nanoparticle uptake in tumor cells: combination of magnetically induced cell labeling and magnetic heating]. / Magnetisch basierte Steigerung der Nanopartikelaufnahme in Tumorzellen: Kombination von magnetisch induzierter Zellmarkierung und magnetischer Wärmebehandlung.

PURPOSE: Magnetic nanoparticles (MNP) are known to be versatile tools in diagnostic and interventional radiology. The goal of the present study was to assess whether MNP can be selectively accumulated on human adenocarcinoma cells in vitro using an external magnetic field (magnetically induced cell labeling) and whether these labeled tumor cells can then be destroyed after being exposed to an alternating magnetic field (magnetically induced heating). In this context, a long-term goal is to combine these two developing methods to achieve an additive effect in tumor therapy. MATERIALS AND METHODS: BT-474 cells were incubated until confluence. Magnetic nanoparticles (0.32 mg Fe/ml culture medium) were then added and the flask was exposed to an external magnetic field gradient (magnetically induced cell labeling, 56 or 83 mT magnets) for 24 hours in order to label the tumor cells with nanoparticles. Cells without both MNP and magnetic labeling as well as cells with MNP incubation but without magnetic labeling served as controls. After MNP incubation, the magnetically labeled cells (5 x 10 (7) cells/ml) were exposed to an alternating magnetic field for 5.45 minutes (frequency 400 kHz, amplitude 24.6 kA/m). The combination effect of both magnetic labeling and magnetic heating was assessed by determining the temperature increase. The amount of MNP accumulated within the cells was determined by measuring the iron content via atomic absorption spectrometry. For statistical analysis mean values and standard deviations of temperature increases and iron contents were calculated and the differences were analyzed using the Student's t-test. RESULTS: A significant temperature increase (p < 0.01) during magnetic heating of 41.76 +/- 4.60 K was detected after magnetic labeling of the cells (5 x 10 (7) cells/ml, 83 mT) incubated with MNP. In comparison, the cells incubated with MNP but without magnetic labeling revealed a temperature increase of 32.03 +/- 3.33 K, naked cells of only 2.69 +/- 0.34 K. CONCLUSION: The results demonstrated the magnetically based enhancement of cellular uptake of nanoparticles by tumor cells, resulting in the intensification of the generated temperature increase during magnetic heating. Consequently, magnetic nanoparticles are shown to be valuable tools for the combination of magnetically based therapy modalities.

Magnetorelaxometry for localization and quantification of magnetic nanoparticles for thermal ablation studies.

In magnetic heating treatments, intratumorally injected superparamagnetic iron oxide nanoparticles (MNP) exposed to an externally applied alternating magnetic field generate heat, specifically at the tumor region. This inactivates cancer cells with minimal side effects to the normal tissue. Therefore, the quantity of MNP needs to be thoroughly controlled to govern adequate heat production. Here, we demonstrate the capability of magnetorelaxometry (MRX) for the non-invasive quantification and localization of MNP accumulation in small animal models. The results of our MRX measurements using a multichannel vector magnetometer system with 304 SQUIDs (superconductive quantum interference device) on three mice hosting different carcinoma models (9L/lacZ and MD-AMB-435) are presented. The position and magnitude of the magnetic moment are reconstructed from measured spatial magnetic field distributions by a magnetic dipole model fit applying a Levenberg-Marquadt algorithm. Therewith, the center of gravity and the total amount of MNP accumulation in the mice are determined. Additionally, for a fourth mouse the distribution of MNP over individual organs and the tumor is analyzed by single-channel SQUID measurements, obtaining a sensitive spatial quantification. This study shows that magnetorelaxometry is well suited to monitor MNP accumulation before cancer therapy, with magnetic heating being an important precondition for treatment success.