Biophysical Characterization of (Silica-coated) Cobalt Ferrite Nanoparticles for Hyperthermia Treatment

Magnetic hyperthermia is a technique that describes the heating of material through an external magnetic field. Classic hyperthermia is a medical condition where the human body overheats, being usually triggered by a heat stroke, which can lead to severe damage to organs and tissue due to the denaturation of cells. In modern medicine, hyperthermia can be deliberately induced to specified parts of the body to destroy malignant cells. Magnetic hyperthermia describes the way that this overheating is induced and it has the inherent advantage of being a minimal invasive method when compared to traditional surgery methods. This work presents a particle system that offers huge potential for hyperthermia treatments, given its good loss value, i.e., the particles dissipate a lot of heat to their surroundings when treated with an ac magnetic field. The measurements were performed in a low-cost custom hyperthermia setup. Additional toxicity assessments on Jurkat cells show a very low short-term toxicity on the particles and a moderate low toxicity after two days due to the prevalent health concerns towards nanoparticles in organisms

Spektroskopie und Bildgebung magnetischer Nanopartikel: Eine multiparametrische Analyse von Partikel-Matrix-Wechselwirkungen

This work comprises a multiparametric analysis of particle-matrix interactions using magnetic particle spectroscopy (MPS) and the corresponding imaging modality magnetic particle imaging (MPI). To investigate particle-matrix interactions, the dynamic magnetization response of magnetic nanoparticles to externally applied alternating magnetic fields is evaluated. Due to the nonlinear magnetization characteristics of magnetic nanoparticles, the higher harmonics of the magnetization resulting from the periodic excitation in particular serve as source of information. The measurements presented were realized with a temperature-controlled MPS setup implemented as part of this work. For multiparametric investigations, measurement parameters such as the magnetic field strength of the externally applied field, the excitation frequency, the sample temperature, the dynamic viscosity of the medium surrounding the particles or particle systems and related properties were varied. Based on the results, conclusions are drawn about physical relationships and the quantifiability of measurement results and their transferability to the MPI imaging technique are discussed. It is shown that particle-matrix interactions in MPS can be resolved in the millisecond range. Temperature-dependent measurement results are traced back to the dominant relaxation mechanism of the used particle system. With the help of Fokker-Planck simulations, the structure of multicore particles is clarified from a viscosity series based on CoFe2O4 particles. Furthermore, the influence of the dynamic viscosity on the measurement data is discussed. Magnetization curves reconstructed from the measurement data are used to analyze thermal interactions with the carrier medium. Furthermore, the spectral decomposition of the magnetization harmonics is introduced and applied to derive temperature and viscosity dependent mapping functions. Due to the degree of similarity of the measurement principles, the findings from experimental MPS data can be transferred to the MPI imaging method in order to assess and validate the quantifiability of the method. Dilution series of particle suspensions serve to characterize both the MPS setup and the institute’s custom-built dual-frequency MPI scanner. Finally, realized 2D and 3D MPI measurement results are shown and dual-frequency mobility MPI data of different viscosity levels are presented.Diese Arbeit umfasst eine multiparametrische Analyse von Partikel-Matrix-Wechselwirkungen unter der Verwendung der Methode Magnetic Particle Spectroscopy (MPS) und der Bildgebungsmodalität Magnetic Particle Imaging (MPI). Zur Untersuchung wird die dynamische Magnetisierungsantwort magnetischer Nanopartikel auf externe magnetische Wechselfelder ausgewertet. Aufgrund der nichtlinearen Magnetisierungskennlinie der magnetischen Nanopartikel dienen insbesondere die aus der periodischen Anregung resultierenden höheren Harmonischen der Magnetisierung als Informationsquelle. Die vorgestellten Messungen wurden mit einem im Rahmen der Arbeit umgesetzten temperaturgeregelten MPS-Aufbau realisiert. Für die multiparametrischen Untersuchungen wurden Messparameter wie die magnetische Feldstärke des extern angelegten Feldes, die Anregungsfrequenz, die Probentemperatur, die dynamische Viskosität des die Partikel umgebenden Mediums oder Partikeleigenschaften, bzw. -systeme variiert. Anhand der Ergebnisse werden Rückschlüsse auf physikalische Zusammenhänge getätigt und die Quantifizierbarkeit von Messergebnissen sowie deren Übertragbarkeit auf das Bildgebungsverfahren MPI diskutiert. Es wird gezeigt, dass Partikel-Matrix-Wechselwirkungen im MPS im Millisekundenbereich aufgelöst werden können. Temperaturabhängige Messergebnisse werden auf den dominierenden Relaxationsmechanismus des vorliegenden Partikelsystems zurückgeführt. Unter Zuhilfenahme von Fokker-Planck -Simulationen wird aus einer auf CoFe2O4 -Partikeln basierenden Viskositätsserie der strukturelle Aufbau von Multikernpartikeln aufgeklärt und der Einfluss der dynamischen Viskosität auf die Messdaten diskutiert. Aus den Messdaten rekonstruierte Magnetisierungskurven dienen der Analyse von thermischen Interaktionen mit dem Trägermedium. Die spektrale Zerlegung der Magnetisierungsharmonischen wird eingeführt und angewendet, um temperatur- und viskositätsabhängige Abbildungsfunktionen abzuleiten. Aufgrund des Verwandschaftsgrades der Messprinzipien können die Erkenntnisse aus experimentellen MPS-Daten auf das Bildgebungsverfahren MPI übertragen werden, um die Quantifizierbarkeit der Methode zu beurteilen und zu validieren. Verdünnungsserien von Partikelsuspensionen dienen der Charakterisierung beider Systeme, der des MPS-Aufbaus und der des am Institut gefertigten Zwei-Frequenz-MPIScanners. Abschließend werden im Rahmen der Arbeit realisierte 2D und 3D MPI-Messergebnisse gezeigt und Zwei-Frequenz-mobility-MPI-Daten von Viskositätsstufen vorgestellt

Modeling the impedance of water-cooled core-less multi-layered solenoid coils for MPI drive field generation

A complete lumped component model representing the wideband impedance of water-cooled multi-layered core-less solenoid coils is presented and analytical and numerical calculation methods for model elements are reviewed and extended. The model includes stray capacitances, mutual inductances and frequency-dependent resistive losses. Contrary to previous treatments of this topic, the model is not simplified further and is evaluated in its complete form, allowing accurate prediction of the coil impedance beyond the first resonant frequency. This aspect is especially important if the coil is part of a passive filter circuit, where higher resonances limit the filter bandwidth. Also, a liquid coolant is included in the calculations.Additionally, figures of merit for the evaluation of field homogeneity inside the coil are given.The model is applied to a MPI drive coil and is compared to measured data. It shows good agreement up to 4 MHz, including the second series resonance of the coil. Additionally, the influence of water-cooling on the coil impedance is investigated. Comparison of model results to measured data shows additional losses.Int. J. Mag. Part. Imag. 4(1), 2018, Article ID: 1804001, DOI: 10.18416/IJMPI.2018.180400

Temperature-dependent MPS measurements

The non-linear signal generation in Magnetic Particle Imaging (MPI) using magnetic nanoparticles as tracer materials is still not fully explained and a far-reaching research area. Magnetic Particle Spectroscopy (MPS) was developed to investigate the particle behavior in high externally applied magnetic field strengths and to derive mathematical models which describe the physical processes in MPI in detail. A new MPS setup was built which allows measurements between -13 °C and +114 °C in order to investigate the temperature dependence of the harmonics spectra. Temperature-dependent MPS measurements of diluted FeraSpinTM XL, either as suspension or freeze-dried in a mannitol matrix, using the new setup are shown and exemplarily discussed

Initial imaging experiments with a direct-driven relaxation Magnetic Particle Imaging setup

This contribution presents initial imaging experiments with a newly designed imaging setup that facilitates Magnetic Particle Imaging (MPI) by recording the step response of the tracer in contrast to its higher harmonic spectrum. Such a concept promises a greatly reduced complexity in hardware and enables a much simpler time-domain evaluation of the receive signals. The concept borrows from magnetorelaxometry (MRX) subjecting the tracer to a step change in excitation field to affect a relaxation of the particles’ magnetization. For that reason, all experience from MRX data evaluation and modeling of the magnetization response apply to the imaging variant as well. The hardware design of the system opens a great deal of flexibility regarding excitation patterns and signal evaluation for future experiments.   Int. J. Mag. Part. Imag. 6(2), Suppl. 1, 2020, Article ID: 2009060, DOI: 10.18416/IJMPI.2020.200906

Cellular effects of paclitaxel-loaded iron oxide nanoparticles on breast cancer using different 2D and 3D cell culture models

Background: Magnetic drug targeting (MDT) is an effective alternative for common drug applications, which reduces the systemic drug load and maximizes the effect of, eg, chemotherapeutics at the site of interest. After the conjugation of a magnetic carrier to a chemotherapeutic agent, the intra-arterial injection into a tumor-afferent artery in the presence of an external magnetic field ensures the accumulation of the drug within the tumor tissue. Materials and methods: In this study, we used superparamagnetic iron oxide nanoparticles (SPIONs) coated with lauric acid and human serum albumin as carriers for paclitaxel (SPIONLA-HSA-Ptx). To investigate whether this particle system is suitable for a potential treatment of cancer, we investigated its physicochemical properties by dynamic light scattering, ζ potential measurements, isoelectric point titration, infrared spectroscopy, drug release quantification, and magnetic susceptibility measurements. The cytotoxic effects were evaluated using extensive toxicological methods using flow cytometry, IncuCyte® live-cell imaging, and growth experiments on different human breast cancer cell lines in two- and three-dimensional cell cultures. Conclusion: The data showed that next to their high magnetization capability, SPIONLA-HSA-Ptx have similar cytostatic effects on human breast cancer cells as pure paclitaxel, suggesting their usage for future MDT-based cancer therapy