In this work, we present the arrangement of Fe3O4 magnetic nanoparticles into 3D linear chains and its effect on magnetic particle hyperthermia efficiency. The alignment has been performed under a 40 mT magnetic field in an agarose gel matrix. Two different sizes of magnetite nanoparticles, 10 and 40 nm, have been examined, exhibiting room temperature superparamagnetic and ferromagnetic behavior, in terms of DC magnetic field, respectively. The chain formation is experimentally visualized by scanning electron microscopy images. A molecular Dynamics anisotropic diffusion model that outlines the role of intrinsic particle properties and inter-particle distances on dipolar interactions has been used to simulate the chain formation process. The anisotropic character of the aligned samples is also reflected to ferromagnetic resonance and static magnetometry measurements. Compared to the non-aligned samples, magnetically aligned ones present enhanced heating efficiency increasing specific loss power value by a factor of two. Dipolar interactions are responsible for the chain formation of controllable density and thickness inducing shape anisotropy, which in turn enhances magnetic particle hyperthermia efficiency.
Recent investigations have attempted to understand and exploit the impact of magnetic field-actuated internalized magnetic nanoparticles (MNPs) on the proliferation rate of cancer cells. Due to the complexity of the parameters governing magnetic field-exposure though, individual studies to date have raised contradictory results. In our approach we performed a comparative analysis of key parameters related to the cell exposure of cancer cells to magnetic field-actuated MNPs, and to the magnetic field, in order to better understand the factors affecting cellular responses to magnetic field-stimulated MNPs. We used magnetite MNPs with a hydrodynamic diameter of 100 nm and studied the proliferation rate of MNPs-treated versus untreated HT29 human colon cancer cells, exposed to either static or alternating low frequency magnetic fields with varying intensity (40-200 mT), frequency (0-8 Hz) and field gradient. All three parameters, field intensity, frequency, and field gradient affected the growth rate of cells, with or without internalized MNPs, as compared to control MNPs-untreated and magnetic field-untreated cells. We observed that the growth inhibitory effects induced by static and rotating magnetic fields were enhanced by pre-treating the cells with MNPs, while the growth promoting effects observed in alternating field-treated cells were weakened by MNPs. Compared to static, rotating magnetic fields of the same intensity induced a similar extend of cell growth inhibition, while alternating fields of varying intensity (70 or 100 mT) and frequency (0, 4 or 8 Hz) induced cell proliferation in a frequency-dependent manner. These results, highlighting the diverse effects of mode, intensity, and frequency of the magnetic field on cell growth, indicate that consistent and reproducible results can be achieved by controlling the complexity of the exposure of biological samples to MNPs and external magnetic fields, through monitoring crucial experimental parameters. We demonstrate that further research focusing on the accurate manipulation of the aforementioned magnetic field exposure parameters could lead to the development of successful non-invasive therapeutic anticancer approaches.
Last decade, three-dimensional printing technology has emerged as a useful tool for meticulously fabricated scaffolds with high precision and accuracy, resulting in intricately detailed biomimetic 3D structures. To this end, nowadays, magnetic scaffolds are becoming increasingly attractive in tissue engineering, due to their ability not only to promote bone tissue formation, bone repair, and regeneration, but at the same time allow for nanoscale drug delivery. Although there has been a lot of research effort on the fabrication of bone scaffolds in the last few years, their perspectives as multifunctional magnetic hyperthermia agents remain an open issue. This emerging, uninvestigated research field requires a carefully designed framework to produce reliable results. This work focuses on establishing such a framework by proposing a standardization protocol with certain experimental steps for an accurate evaluation of the heating efficiency of the 3D printed magnetic scaffolds bone phantoms. The specific indexes of specific absorption rate and specific loss power are carefully determined and calculated here to enhance the differences in the heating experimental approaches that followed until now between magnetic nanoparticles and magnetic bone scaffolds. Meanwhile, the heating evaluation cases that one can find in magnetic hyperthermia are seperatelly defined and analyzed with their suited experimental protocols. Firstly, 3D printed magnetic scaffolds are designed and fabricated. Secondly, they are evaluated as heating carriers. A reliable estimation sequence of the heating efficiency, i.e., the specific absorption rate of the magnetic scaffolds, is introduced, analyzed and discussed in conjunction with the specific loss power, which is the respective quantitative index for evaluating the magnetic nanoparticles’ heating efficacy. Finally, this work proposes how the fabrication procedure of the three-dimensional printed scaffolds can be guided by the magnetic particle hyperthermia literature results, as to increase the scaffolds heating efficiency through printing parameters.
Objective: In magnetic particle hyperthermia, a promising least-invasive cancer treatment, malignant regions in proximity with magnetic nanoparticles undergo heat stress, while unavoidably surrounding healthy tissues may also suffer from heat either directly or indirectly by the induced eddy currents, due to the developed electric fields as well. Here, we propose a facile upgrade of a typical magnetic particle hyperthermia protocol, to selectively mitigate eddy currents' heating without compromising the beneficial role of heating in malignant regions. Method:The key idea is to apply the external magnetic field intermittently (in an ON/OFF pulse mode), instead of the continuous field mode typically applied. The parameters of the intermittent field mode, such as time intervals (ON time: 25-100 s, OFF time: 50-200 s, Duty Cycle:16-100%) and field amplitude (30-70 mT) are optimized based on evaluation on healthy tissue and cancer tissue phantoms. The goal is to sustain in cancer tissue phantom the maximum temperature increase (preferably within 4-8 C above body temperature of 37 C), while in the healthy tissue phantom temperature variation is suppressed far below the 4 C dictating the eddy current mitigation. Results: Optimum conditions of intermittent field (ON/OFF: 50/100 in s, Duty Cycle: 33%, magnetic field: 45mT) are then examined in ex-vivo samples verifying the successful suppression of eddy currents. Simultaneously, a well-elaborated theoretical approach provides a rapid calculation of temperature increase and, furthermore, the ability to quickly simulate a variety of duty cycle times and field controls may save experimental time. Conclusion: Eventually, the application of an intermittent field mode in a magnetic particle hyperthermia protocol, succeeds in eddy current mitigation in surrounding tissues and allows for the application of larger field amplitudes that may augment hyperthermia efficiency without objecting typical biomedical applicability field constraints such as Brezovich criterion.
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