Iron Oxide Nanorings and Nanotubes for Magnetic Hyperthermia: The Problem of Intraparticle Interactions

Magnetic interactions can play an important role in the heating efficiency of magnetic nanoparticles. Although most of the time interparticle magnetic interactions are a dominant source, in specific cases such as multigranular nanostructures intraparticle interactions are also relevant and their effect is significant. In this work, we have prepared two different multigranular magnetic nanostructures of iron oxide, nanorings (NRs) and nanotubes (NTs), with a similar thickness but different lengths (55 nm for NRs and 470 nm for NTs). In this way, we find that the NTs present stronger intraparticle interactions than the NRs. Magnetometry and transverse susceptibility measurements show that the NTs possess a higher effective anisotropy and saturation magnetization. Despite this, the AC hysteresis loops obtained for the NRs (0?400 Oe, 300 kHz) are more squared, therefore giving rise to a higher heating efficiency (maximum specific absorption rate, SARmax = 110 W/g for the NRs and 80 W/g for the NTs at 400 Oe and 300 kHz). These results indicate that the weaker intraparticle interactions in the case of the NRs are in favor of magnetic hyperthermia in comparison with the NTs.This research was funded by the Vietnam National Foundation for Science and Technology Development (NAFOSTED), grant number 103.02-2019.314. The Spanish Government is acknowledged for the “Nanotechnology in translational hyperthermia (HIPERNANO)” research network (RED2018-102626-T) and for funding under the project number MAT2017-83631-C3. Research at USF was supported by US Department of Energy, Office of Basic Energy Sciences, Division of Materials Science and Engineering, Award No. DE-FG02-07ER46438. Basque Government is also acknowledged for funding under the project number IT-1005-16 and for the postdoctoral fellowship POS_2020_1_0028

Magnetic Vortex and Hyperthermia Suppression in Multigrain Iron Oxide Nanorings

Single-crystal iron oxide nanorings have been proposed as a promising candidate for magnetic hyperthermia application because of their unique shape-induced vortex-domain structure, which supports good colloidal stability and enhanced magnetic properties. However, the synthesis of single crystalline iron oxide has proven to be challenging. In this article, we showed that chemically synthesized multigrain magnetite nanorings disfavor a shape-induced magnetic vortex-domain structure. Our results indicate that the multigrain Fe3O4 nanorings with an average outer diameter of ~110 nm and an inner to outer diameter ratio of ~0.5 do not show a shape-induced vortex-domain structure, which was observed in the single-crystal Fe3O4 nanorings of similar dimensions. At 300 Ks, multigrain magnetite nanorings showed an effective anisotropy field of 440 Oe, which can be attributed to its high surface area and intraparticle interaction. Both calorimetric and AC loop measurements showed a moderate inductive heating efficiency of multigrain magnetite nanorings of ~300 W/g at 800 Oe. Our results shed light on the magnetic ground states of chemically synthesized multigrain Fe3O4 nanorings

Preparation of Selenium-Based Drug-Modified Polymeric Ligand-Functionalised Fe3O4 Nanoparticles as Multimodal Drug Carrier and Magnetic Hyperthermia Inductor

In recent years, much effort has been invested into developing multifunctional drug delivery systems to overcome the drawbacks of conventional carriers. Magnetic nanoparticles are not generally used as carriers but can be functionalised with several different biomolecules and their size can be tailored to present a hyperthermia response, allowing for the design of multifunctional systems which can be active in therapies. In this work, we have designed a drug carrier nanosystem based on Fe3O4 nanoparticles with large heating power and 4-amino-2-pentylselenoquinazoline as an attached drug that exhibits oxidative properties and high selectivity against a variety of cancer malignant cells. For this propose, two samples composed of homogeneous Fe3O4 nanoparticles (NPs) with different sizes, shapes, and magnetic properties have been synthesised and characterised. The surface modification of the prepared Fe3O4 nanoparticles has been developed using copolymers composed of poly(ethylene-alt-maleic anhydride), dodecylamine, polyethylene glycol and the drug 4-amino-2-pentylselenoquinazoline. The obtained nanosystems were properly characterised. Their in vitro efficacy in colon cancer cells and as magnetic hyperthermia inductors was analysed, thereby leaving the door open for their potential application as multimodal agents

Challenges and Recommendations for Magnetic Hyperthermia Characterization Measurements

The localized heating of magnetic nanoparticles (MNPs) via the application of time-varying magnetic fields – a process known as magnetic field hyperthermia (MFH) – can greatly enhance existing options for cancer treatment; but for broad clinical uptake its optimization, reproducibility and safety must be comprehensively proven. As part of this effort, the quantification of MNP heating – characterized by the specific loss power (SLP), measured in W/g, or by the intrinsic loss power (ILP), in nHm2/kg – is frequently reported. However, in SLP/ILP measurements to date, the apparatus, the analysis techniques and the field conditions used by different researchers have varied greatly, leading to questions as to the reproducibility of the measurements. To address this, we report here on an interlaboratory study (across N = 21 European sites) of calorimetry measurements that constitutes a snapshot of the current state-of-the-art within the MFH community. The data show that although there is very good intralaboratory repeatability, the overall interlaboratory measurement accuracy is poor, with the consolidated ILP data having standard deviations on the mean of ca. ± 30% to ± 40%. There is a strong systematic component to the uncertainties, and a clear rank correlation between the measuring laboratory and the ILP. Both of these are indications of a current lack of normalization in this field. A number of possible sources of systematic uncertainties are identified, and means determined to alleviate or minimize them. However, no single dominant factor was identified, and significant work remains to ascertain and remove the remaining uncertainty sources. We conclude that the study reveals a current lack of harmonization in MFH characterization of MNPs, and highlights the growing need for standardized, quantitative characterization techniques for this emerging medical technology.Multifunctional Nanoparticles for Magnetic Hyperthermia and Indirect Radiation Therap

Harmonic phases of the nanoparticle magnetization: An intrinsic temperature probe

Magnetic fluid hyperthermia is a promising cancer therapy in which magnetic nanoparticles act as heat sources activated by an external AC magnetic field. The nanoparticles, located near or inside the tumor, absorb energy from the magnetic field and then heat up the cancerous tissues. During the hyperthermia treatment, it is crucial to control the temperature of different tissues: too high temperature can cause undesired damage in healthy tissues through an uncontrolled necrosis. However, the current thermometry in magnetic hyperthermia presents some important technical problems. The widely used optical fiber thermometers only provide the temperature in a discrete set of spatial points. Moreover, surgery is required to locate these probes in the correct place. In this scope, we propose here a method to measure the temperature of a magnetic sample. The approach relies on the intrinsic properties of the magnetic nanoparticles because it is based on monitoring the thermal dependence of the high order harmonic phases of the nanoparticle dynamic magnetization. The method is non-invasive and it does not need any additional probe or sensor attached to the magnetic nanoparticles. Moreover, this method has the potential to be used together with the magnetic particle imaging technique to map the spatial distribution of the temperature

In Vivo Imaging of Local Gene Expression Induced by Magnetic Hyperthermia

The present work aims to demonstrate that colloidal dispersions of magnetic iron oxide nanoparticles stabilized with dextran macromolecules placed in an alternating magnetic field can not only produce heat, but also that these particles could be used in vivo for local and noninvasive deposition of a thermal dose sufficient to trigger thermo-induced gene expression. Iron oxide nanoparticles were first characterized in vitro on a bio-inspired setup, and then they were assayed in vivo using a transgenic mouse strain expressing the luciferase reporter gene under transcriptional control of a thermosensitive promoter. Iron oxide nanoparticles dispersions were applied topically on the mouse skin or injected subcutaneously with Matrigel™ to generate so-called pseudotumors. Temperature was monitored continuously with a feedback loop to control the power of the magnetic field generator and to avoid overheating. Thermo-induced luciferase expression was followed by bioluminescence imaging 6 h after heating. We showed that dextran-coated magnetic iron oxide nanoparticle dispersions were able to induce in vivo mild hyperthermia compatible with thermo-induced gene expression in surrounding tissues and without impairing cell viability. These data open new therapeutic perspectives for using mild magnetic hyperthermia as noninvasive modulation of tumor microenvironment by local thermo-induced gene expression or drug release.Magnéto-Chimiothérapie : Modélisation de la Délivrance Induite par Champ Magnétique Radiofréquence d'Anticancéreux par des Nano-Vésicules Polymères et Suivi par IRM d'un Modèle de GlioblastomeTranslational Research and Advanced Imaging LaboratoryMultifunctional Nanoparticles for Magnetic Hyperthermia and Indirect Radiation Therap

A wide-frequency range AC magnetometer to measure the specific absorption rate in nanoparticles for magnetic hyperthermia

Measurement of specific absorption rate (SAR) of magnetic nanoparticles is crucial to assert their potential for magnetic hyperthermia. To perform this task, calorimetric methods are widely used. However, those methods are not very accurate and are difficult to standardize. In this paper, we present AC magnetometry results performed with a lab made magnetometer that is able to obtain dynamic hysteresis loops in the AC magnetic field frequency range from 50 kHz to 1 MHz and intensities up to 24 kA m(-1) In this work, SAR values of maghemite nanoparticles dispersed in water are measured by AC magnetometry. The so obtained values are compared with the SAR measured by calorimetric methods. Both measurements, by calorimetry and magnetometry, are in good agreement. Therefore, the presented AC magnetometer is a suitable way to obtain SAR values of magnetic nanoparticles. (C) 2013 Elsevier B.V. All rights reserved

Fundamentals and advances in magnetic hyperthermia

Nowadays, magnetic hyperthermia constitutes a complementary approach to cancer treatment. The use of magnetic particles as heating mediators, proposed in the 1950s, provides a novel strategy for improving tumor treatment and, consequently, patient's quality of life. This review reports a broad overview about several aspects of magnetic hyperthermia addressing new perspectives and the progress on relevant features such as the ad hoc preparation of magnetic nanoparticles, physical modeling of magnetic heating, methods to determine the heat dissipation power of magnetic colloids including the development of experimental apparatus and the influence of biological matrices on the heating efficiency.Multifunctional Nanoparticles for Magnetic Hyperthermia and Indirect Radiation Therap

Exploring the potential of the dynamic hysteresis loops via high field, high frequency and temperature adjustable AC magnetometer for magnetic hyperthermia characterization

Aim The Specific Absorption Rate (SAR) is the key parameter to optimize the effectiveness of magnetic nanoparticles in magnetic hyperthermia. AC magnetometry arises as a powerful technique to quantify the SAR by computing the hysteresis loops' area. However, currently available devices produce quite limited magnetic field intensities, below 45mT, which are often insufficient to obtain major hysteresis loops and so a more complete and understandable magneticcharacterization. This limitation leads to a lack of information concerning some basic properties, like the maximum attainable (SAR) as a function of particles' size and excitation frequencies, or the role of the mechanical rotation in liquid samples. Methods To fill this gap, we have developed a versatile high field AC magnetometer, capable of working at a wide range of magnetic hyperthermia frequencies (100 kHz – 1MHz) and up to field intensities of 90mT. Additionally, our device incorporates a variable temperature system for continuous measurements between 220 and 380 K. We have optimized the geometrical properties of the induction coil that maximize the generated magnetic field intensity. Results To illustrate the potency of our device, we present and model a series of measurements performed in liquid and frozen solutions of magnetic particles with sizes ranging from 16 to 29 nm. Conclusion We show that AC magnetometry becomes a very reliable technique to determine the effective anisotropy constant of single domains, to study the impact of the mechanical orientation in the SAR and to choose the optimal excitation parameters to maximize heating production under human safety limits