Role of anisotropy, frequency, and interactions in magnetic hyperthermia applications: noninteracting nanoparticles and linear chain arrangements

Efforts by numerous research groups have provided a deeper insight into the physical mechanisms behind the power absorption of single-domain magnetic nanoparticles in magnetic-fluid-hyperthermia applications and theoretical models now account for the main experimental observations. However, the role of all parameters relevant to the magnetic relaxation remains a matter of debate. Here, we employ a nonlinear model for the magnetic relaxation of single-domain magnetic nanoparticles with uniaxial effective anisotropy and evaluate the influence of particle-intrinsic parameters as well as experimental conditions on the power absorption of both noninteracting and interacting systems (linear arrangements). These effects are assessed through the enclosed hysteresis area of the magnetization loops as a function of relative anisotropy hK (the anisotropy field with respect to the amplitude of the ac field), i.e., the "area curve"of the system. These curves can be divided into four regions with distinct magnetic responses and boundaries that depend on the particle size, frequency of the applied field and interactions. Interactions change the effective anisotropy of the system and shift the area curve towards lower hK values. For the low relative anisotropy range, dipolar interactions increase the area of the hysteresis loops [thus, the specific power absorption (SPA)], while they are detrimental or produce nonsignificant effects for the range of high relative anisotropy. Our study resolves seemingly contradictory results of interaction effects in linear arrangements recently reported in the literature. Simulations of randomly oriented particles and chains were contrasted with the oriented cases. An analytical approach and the thermal interpretation of its validity range are discussed, both aimed at the design of nanoparticles and the choice of the experimental conditions for optimal heating. We find that systems with low-thermal-fluctuation influence are better candidates for the application due to their high SPA values. © 2021 American Physical Society

Circulating and Tumor-Associated Neutrophils in the Era of Immune Checkpoint Inhibitors: Dynamics, Phenotypes, Metabolism, and Functions.

Neutrophils are the most abundant myeloid cells in the blood and are a considerable immunological component of the tumor microenvironment. However, their functional importance has often been ignored, as they have always been considered a mono-dimensional population of terminally differentiated, short-living cells. During the last decade, the use of cutting-edge, single-cell technologies has revolutionized the classical view of these cells, unmasking their phenotypic and functional heterogeneity. In this review, we summarize the emerging concepts in the field of neutrophils in cancer, by reviewing the recent literature on the heterogeneity of both circulating neutrophils and tumor-associated neutrophils, as well as their possible significance in tumor prognosis and resistance to immune checkpoint inhibitors

Low-Dimensional Assemblies of Magnetic MnFe2O4 Nanoparticles and Direct In Vitro Measurements of Enhanced Heating Driven by Dipolar Interactions: Implications for Magnetic Hyperthermia

Magnetic fluid hyperthermia (MFH), the procedure of raising the temperature of tumor cells using magnetic nanoparticles (MNPs) as heating agents, has proven successful in treating some types of cancer. However, the low heating power generated under physiological conditions makes it necessary a high local concentration of MNPs at tumor sites. Here, we report how the in vitro heating power of magnetically soft MnFe2O4 nanoparticles can be enhanced by intracellular low-dimensional clusters through a strategy that includes: (a) the design of the MNPs to retain Neel magnetic relaxation in high-viscosity media, and (b) culturing MNP-loaded cells under magnetic fields to produce elongated intracellular agglomerates. Our direct in vitro measurements demonstrated that the specific loss power (SLP) of elongated agglomerates (SLP = 576 +/- 33 W/g) induced by culturing BV2 cells in situ under a dc magnetic field was increased by a factor of 2 compared to the SLP = 305 +/- 25 W/g measured in aggregates freely formed within cells. A numerical mean-field model that included dipolar interactions quantitatively reproduced the SLPs of these clusters both in phantoms and in vitro, suggesting that it captures the relevant mechanisms behind power losses under high-viscosity conditions. These results indicate that in situ assembling of MNPs into low-dimensional structures is a sound possible way to improve the heating performance in MFH

Adjusting the Neel relaxation time of Fe3O4/ZnxCo1-xFe2O4 core/shell nanoparticles for optimal heat generation in magnetic hyperthermia

In this work it is shown a precise way to optimize the heat generation in high viscosity magnetic colloids, by adjusting the Neel relaxation time in core/shell bimagnetic nanoparticles, for magnetic fluid hyperthermia (MFH) applications. To pursue this goal, Fe3O4/ZnxCo1-xFe2O4 core/shell nanoparticles were synthesized with 8.5 nm mean core diameter, encapsulated in a shell of similar to 1.1 nm of thickness, where the Zn atomic ratio (Zn/(Zn + Co) at%) changes from 33 to 68 at%. The magnetic measurements are consistent with a rigid interface coupling between the core and shell phases, where the effective magnetic anisotropy systematically decreases when the Zn concentration increases, without a significant change of the saturation magnetization. Experiments of MFH of 0.1 wt% of these particles dispersed in water, in Dulbecco modified Eagles minimal essential medium, and a high viscosity butter oil, result in a large specific loss power (SLP), up to 150 W g(-1), when the experiments are performed at 571 kHz and 200 Oe. The SLP was optimized adjusting the shell composition, showing a maximum for intermediate Zn concentration. This study shows a way to maximize the heat generation in viscous media like cytosol, for those biomedical applications that require smaller particle sizes

Controlling the dominant magnetic relaxation mechanisms for magnetic hyperthermia in bimagnetic core-shell nanoparticles

We report a simple and effective way to control the heat generation of a magnetic colloid under alternate magnetic fields by changing the shell composition of bimagnetic core-shell Fe 3 O 4 /Zn x Co 1-x Fe 2 O 4 nanoparticles. The core-shell structure constitutes a magnetically-coupled biphase system, with an effective anisotropy that can be tuned by the substitution of Co 2+ by Zn 2+ ions in the shell. Magnetic hyperthermia experiments of nanoparticles dispersed in hexane and butter oil showed that the magnetic relaxation is dominated by Brown relaxation mechanism in samples with higher anisotropy (i.e., larger concentration of Co within the shell) yielding high specific power absorption values in low viscosity media as hexane. Increasing the Zn concentration of the shell, diminishes the magnetic anisotropy, which results in a change to a Néel relaxation that dominates the process when the nanoparticles are dispersed in a high-viscosity medium. We demonstrate that tuning the Zn contents at the shell of these exchange-coupled core/shell nanoparticles provides a way to control the magnetic anisotropy without loss of saturation magnetization. This ability is an essential prerequisite for most biomedical applications, where high viscosities and capturing mechanisms are present. This journal i

Magnetic hyperthermia experiments with magnetic nanoparticles in clarified butter oil and paraffin: A thermodynamic analysis

In specific power absorption models for magnetic fluid hyperthermia (MFH) experiments, the magnetic relaxation time of nanoparticles (NPs) is known to be a fundamental descriptor of the heating mechanisms. The relaxation time is mainly determined by the interplay between the magnetic properties of NPs and the rheological properties of NPs’ environment. Although the role of magnetism in MFH has been extensively studied, the thermal properties of the NP medium and their changes during MFH experiments have been underrated so far. Herein, we show that ZnxFe3-xO4 NPs dispersed through different media with phase transition in the temperature range of experiment as clarified butter oil (CBO) and paraffin. These systems show nonlinear behavior of the heating rate within the temperature range of MFH experiments. For CBO, a fast increase at ~306 K is associated with changes in the viscosity (¿(T)) and specific heat (cp(T)) of the medium at its melting temperature. This increment in the heating rate takes place around 318 K for paraffin. The magnetic and morphological characterization of NPs together with the observed agglomeration of NPs above 306 and 318 K for CBO and paraffin, respectively, indicate that the fast increase in MFH curves could not be associated with the change in the magnetic relaxation mechanism, with Neél relaxation being dominant. In fact, successive experimental runs performed up to temperatures below and above the CBO and paraffin melting points resulted in different MFH curves due to agglomeration of NPs driven by magnetic field inhomogeneity during the experiments. Our results highlight the relevance of the thermodynamic properties of the system NP-medium for an accurate measurement of the heating efficiency for in vitro and in vivo environments, where the thermal properties are largely variable within the temperature window of MFH experiments