Magnetic Hyperthermia Applications Research Articles

Effect of precipitating agent, N2 gas, extract volume and pH on the magnetic properties of magnetite nanoparticles by green synthesis from aqueous pomegranate peel extract

Superparamagnetic nanoparticles (SPMNPs) have attracted considerable attention in biomedicine, particularly magnetic hyperthermia for cancer treatment. However, the development of efficient and eco-friendly methods for synthesizing SPMNPs remains a challenge. This study reports on a green synthesis approach for SPMNPs using pomegranate peel extract as a stabilizing agent. The effects of various synthesis parameters, including the type of precipitating agent (NH3 and NaOH), N2 gas, extract volume, and pH, were systematically investigated with regard to the size, morphology, and magnetic properties of the nanoparticles. The results showed that reducing the volume of the extract increased the saturation magnetization of the nanoparticles. N2 gas was found to be essential in preventing the oxidation of the nanoparticles. The type of precipitating agent also affected the size and magnetization of the nanoparticles, with NaOH leading to the synthesis of SPMNPs with higher magnetization (∼4 times) compared to NH3. Additionally, nanoparticles synthesized at pH 10 exhibited higher magnetization than those synthesized at pH 8 and 12. In conclusion, the optimized synthesis conditions significantly affected the magnetization and stability of SPMNPs. These nanoparticles are suitable for use in magnetic nanofluid hyperthermia applications.

Understanding magnetic hyperthermia performance within the "Brezovich criterion": beyond the uniaxial anisotropy description.

Careful determination of the heating performance of magnetic nanoparticles under AC fields is critical for magnetic hyperthermia applications. However, most interpretations of experimental data are based on the uniaxial anisotropy approximation, which in the first instance can be correlated with the particle aspect ratio. This is to say, the intrinsic magnetocrystalline anisotropy is discarded, under the assumption that the shape contribution dominates. We show in this work that such a premise, generally valid for large field amplitudes, does not hold for describing hyperthermia experiments carried out under small field values. Specifically, given its relevance for in vivo applications, we focus our analysis on the so-called "Brezovich criterion", H·f = 4.85 × 108 A m-1 s-1. By means of a computational model, we show that the intrinsic magnetocrystalline anisotropy plays a critical role in defining the heat output, determining also the role of the shape and aspect ratio of the particles on the SLP. Our results indicate that even small deviations from spherical shape have an important impact on optimizing the heating performance. The influence of interparticle interactions on the dissipated heat is also evaluated. Our results call, therefore, for an improvement in the theoretical models used to interpret magnetic hyperthermia performance.

Control of Anisotropy and Magnetic Hyperthermia Effect by Addition of Cobalt on Magnetite Nanoparticles.

Magnetic hyperthermia (MH) has emerged as a promising technology with diverse applications in medical and technological fields, leveraging the remote induction of temperature elevation through an alternating magnetic field. While Fe3O4 nanoparticles with an average size around 12-25 nm are commonly employed in MH systems, this study introduces a strategy to produce smaller particles (less than or equal to 10 nm) with enhanced heating efficiency, as measured by specific power absorption (SPA). We conducted an exhaustive and detailed investigation into the morphological and magnetic properties of CoxFe3-xO4 nanoparticles, aiming to optimize their MH response. By varying the Co content, we successfully tuned the effective magnetic anisotropy while maintaining saturation magnetization nearly constant. The MH analysis indicates that these nanoparticles predominantly heat through the Néel mechanism, demonstrating robust reproducibility across different concentrations, viscosity mediums, and ac field conditions. Notably, we identified an optimal anisotropy or Co concentration that maximizes SPA, crucial for developing magnetic systems requiring particles with specific sizes. This work contributes to advancing the understanding and application of MH, particularly in tailoring nanoparticle properties for targeted and efficient heat generation in various contexts.

Optimization of the coating process in the PEGylated chitosan-based doped cobalt ferrite nanoparticles for hyperthermia applications using the Taguchi method

In this study, the parameters of coating process in the PEGylated chitosan-based doped cobalt ferrite nanoparticles for hyperthermia applications was optimized using the Taguchi method. The effect of chitosan and polyethylene glycol as well as the glutaraldehyde (crosslinker) contents on the structural, microstructural, and magnetic properties and the colloidal stability of the nanoparticles were investigated. Ultimately, to optimize the properties of the nanoparticles, the Taguchi method (L16 orthogonal array) was employed. The incorporation of the Ca2+ and Gd3+ into the spinel structure with an average crystallite size of 21 nm was successfully verified by X-ray diffraction (XRD) and the Rietveld refinement analysis. Moreover, thermogravimetric (TGA) analysis and Fourier-transform infrared spectroscopy (FT-IR) demonstrated the effective functionalization of the chitosan and polyethylene glycol coatings. Vibrating sample magnetometer (VSM) measurements revealed that saturation magnetization (Ms) was achieved in the range of 54.91–60.42 emu/g. Also, microstructural observations indicated that the coating layer can affect the particle size distribution and morphology. The Taguchi method identified that the glutaraldehyde content is the most expressive parameter influencing the nanoparticles’ properties, with the optimum properties achieved at chitosan, polyethylene glycol, and glutaraldehyde of 0.4 g, 0.08 g, and 1.2 ml, respectively. The antibacterial analysis confirmed the promising potential of the coated nanoparticles for biomedical applications. Furthermore, the magnetic heating efficiency of the synthesized nanoparticles was investigated in various concentrations of magnetic fluid, demonstrating their suitability for magnetic hyperthermia application.

Multicore iron oxide nanoparticles for magnetic hyperthermia and combination therapy against cancer cells

HypothesisMulticore flower-like iron oxide nanoparticles (IONPs) are among the best candidates for magnetic hyperthermia applications against cancers. However, they are rarely investigated in physiological environments and their efficacy against cancer cells has been even less studied. The combination of magnetic hyperthermia, using multicore IONPs, with selected bioactive molecules should lead to an enhanced activity against cancer cells. ExperimentsMulticore IONPs were synthesized by a seeded-growth thermal decomposition approach. Then, the cytotoxicity, cell uptake, and efficacy of the magnetic hyperthermia approach were studied with six cancer cell lines: PANC1 (pancreatic carcinoma), Mel202 (uveal melanoma), MCF7 (breast adenocarcinoma), MB231 (triple-negative breast cancer line), A549 (lung cancer), and HCT116 (colon cancer). Finally, IONPs were modified with a chemotherapeutic drug (SN38) and tumor suppressor microRNAs (miR-34a, miR-182, let-7b, and miR-137), to study their activity against cancer cells with and without combination with magnetic hyperthermia. FindingsTwo types of multicore IONPs with very good heating abilities under magnetic stimulation have been prepared. Their concentration-dependent cytotoxicity and internalization have been established, showing a strong dependence on the cell line and the nanoparticle type. Magnetic hyperthermia causes significant cell death that is dramatically enhanced in combination with the bioactive molecules.

Effect of moringa oleifera with pure and Zn-doped Mn and Ni nanoferrites for hyperthermia applications

Nanoferrites like spinel manganese ferrite (MnFe2O4) and inverse spinel nickel ferrite (NiFe2O4) have an efficient heating deportment to the destruction of neoplasm. The incorporation of Moringa oleifera (MO) leaf extracts with magnetic nanoparticles as heat mediators is an effective approach for treating magnetic hyperthermia. This study investigated the potential heating behavior of bare, Zn-doped MnFe2O4 and NiFe2O4 nanoparticles (NPs) with Moringa oleifera leaf extracts as magnetic hyperthermia agents. High-resolution transmission electron microscopy showed the spherical-like morphology of MnFe2O4 NPs with no impurities in the EDX spectra. X-ray diffraction spectra confirmed the cubic spinel and inverse spinel structure for MnFe2O4 and NiFe2O4 NPs, respectively. Magnetic properties of the prepared nanoferrites exhibit low coercivity values (in the range of 13–18 Oe representing superparamagnetic behavior. Further, the binding energies of the prepared nanoferrites were revealed by X-ray photoelectron spectroscopy. The effective magnetic anisotropy constant (Keff) was calculated to be around 3.9–5.9 kJ/m3 by electron spin resonance. An increased specific surface area (120.69 m2/g) and wider porosity (17.053 nm) were observed for MnFe2O4/MO NPs through Brunauer-Emmett-Teller (BET) analysis. Thermal properties were investigated by measuring the effective specific absorption rate in an alternating magnetic field ranging from 23 to 31 * 10−9 W/g Oe2 Hz. Results indicated that the green synthesized MnFe2O4/MO NPs are promising agents for magnetic hyperthermia applications in cancer therapy.

Synthesis, Surface Modification and Magnetic Properties Analysis of Heat-Generating Cobalt-Substituted Magnetite Nanoparticles.

Here, we present the results of the synthesis, surface modification, and properties analysis of magnetite-based nanoparticles, specifically Co0.047Fe2.953O4 (S1) and Co0.086Fe2.914O4 (S2). These nanoparticles were synthesized using the co-precipitation method at 80 °C for 2 h. They exhibit a single-phase nature and crystallize in a spinel-type structure (space group Fd3¯m). Transmission electron microscopy analysis reveals that the particles are quasi-spherical in shape and approximately 11 nm in size. An observed increase in saturation magnetization, coercivity, remanence, and blocking temperature in S2 compared to S1 can be attributed to an increase in magnetocrystalline anisotropy due to the incorporation of Co ions in the crystal lattice of the parent compound (Fe3O4). The heating efficiency of the samples was determined by fitting the Box-Lucas equation to the acquired temperature curves. The calculated Specific Loss Power (SLP) values were 46 W/g and 23 W/g (under HAC = 200 Oe and f = 252 kHz) for S1 and S2, respectively. Additionally, sample S1 was coated with citric acid (Co0.047Fe2.953O4@CA) and poly(acrylic acid) (Co0.047Fe2.953O4@PAA) to obtain stable colloids for further tests for magnetic hyperthermia applications in cancer therapy. Fits of the Box-Lucas equation provided SLP values of 21 W/g and 34 W/g for CA- and PAA-coated samples, respectively. On the other hand, X-ray photoelectron spectroscopy analysis points to the catalytically active centers Fe2+/Fe3+ and Co2+/Co3+ on the particle surface, suggesting possible applications of the samples as heterogeneous self-heating catalysts in advanced oxidation processes under an AC magnetic field.

Study of biopolymer encapsulated Eu doped Fe3O4 nanoparticles for magnetic hyperthermia application

An exciting prospect in the field of magnetic fluid hyperthermia (MFH) has been the integration of noble rare earth elements (Eu) with biopolymers (chitosan/dextran) that have optimum structures to tune specific effects on magnetic nanoparticles (NPs). However, the heating efficiency of MNPs is primarily influenced by their magnetization, size distribution, magnetic anisotropy, dipolar interaction, amplitude, and frequency of the applied field, the MNPs with high heating efficiency are still challenging. In this study, a comprehensive experimental analysis has been conducted on single-domain magnetic nanoparticles (SDMNPs) for evaluating effective anisotropy, assessing the impact of particle-intrinsic factors and experimental conditions on self-heating efficiency in both noninteracting and interacting systems, with a particular focus on the dipolar interaction effect. The study successfully reconciles conflicting findings on the interaction effects in the agglomeration and less agglomerated arrangements for MFH applications. The results suggest that effective control of dipolar interactions can be achieved by encapsulating Chitosan/Dextran in the synthesized MNPs. The lower dipolar interactions successfully tune the self-heating efficiency and hold promise as potential candidates for MFH applications.

Ca2+ Overload Decreased Cellular Viability in Magnetic Hyperthermia without a Macroscopic Temperature Rise.

Magnetic hyperthermia is a crucial medical engineering technique for treating diseases, which usually uses alternating magnetic fields (AMF) to interplay with magnetic substances to generate heat. Recently, it has been found that in some cases, there is no detectable temperature increment after applying an AMF, which caused corresponding effects surprisingly. The mechanisms involved in this phenomenon are not yet fully understood. In this study, we aimed to explore the role of Ca2+ overload in the magnetic hyperthermia effect without a perceptible temperature rise. A cellular system expressing the fusion proteins TRPV1 and ferritin was prepared. The application of an AMF (518 kHz, 16 kA/m) could induce the fusion protein to release a large amount of iron ions, which then participates in the production of massive reactive oxygen radicals (ROS). Both ROS and its induced lipid oxidation enticed the opening of ion channels, causing intracellular Ca2+ overload, which further led to decreased cellular viability. Taken together, Ca2+ overload triggered by elevated ROS and the induced oxidation of lipids contributes to the magnetic hyperthermia effect without a perceptible temperature rise. These findings would be beneficial for expanding the application of temperature-free magnetic hyperthermia, such as in cellular and neural regulation, design of new cancer treatment methods.

Synthesis and characterization of monophasic MnFe2O4 nanoparticles for potential application in magnetic hyperthermia

Nanostructured materials are being used in a wide range of technological applications. In biomedical applications, magnetic hyperthermia (MH) is a therapeutic modality for the treatment of solid tumors. The materials needed for MH face challenges such as size homogeneity, reasonable temperature increase and biocompatibility. In this work, MnFe2O4 magnetic nanoparticles (Nps) were synthesized by a simple method using the bio-polymer chitosan. Samples with several particles sizes were obtained by treatments at the temperatures of 300, 400, 500 and 600 °C. The particle sizes ranged from 7.8 to 13.3 nm. At 300 K, the saturation magnetization of the Nps varied from 16.2 to 35.8 emu/g. The Mössbauer spectra at low temperatures showed the presence of monophasic MnFe2O4. For all samples, the Mössbauer results at 300 K suggest that the samples are in the superparamagnetic regime. The measurements to obtain the Specific Loss Power (SLP) were conducted at a frequency of 74 kHz and AC field amplitude of 247 Oe. The sample thermally treated at 600 °C and the dispersion prepared with a concentration of 1.0 mg/mL showed the highest SLP of 129.1 W/g.

Development of polymeric nanoparticles associated with SPION and curcumin: a versatile magnetic and fluorescent platform for Life Science applications

Magnetic nanoparticles are prominent in biomedical applications due to their adjustable properties through surface functionalization and inherent magnetism. In the present manuscript, multifunctional nanoparticles were synthesized by combining polymer with a fluorophore and magnetic nanoparticles, resulting in a magnetic and fluorescent nanomaterial. A miniemulsion polymerization technique was employed, using the comonomers methyl methacrylate (MMA) and acrylic acid (AA) in the presence of superparamagnetic iron oxide nanoparticles (SPIONs) and natural turmeric extract (curcumin). Physicochemical characterizations revealed efficient encapsulation of SPIONs within the polymer matrices while maintaining superparamagnetic behavior. The nanosystems exhibited ILP values consistent with those commonly used for magnetic hyperthermia applications, ranging from 0.13 – 0.32 nHm2 kg−1. Additionally, a high fluorescence intensity in the blue/green region was observed, alongside no cell toxicity and substantial internalization in human osteosarcoma cells (OSAS2). Given their intrinsic magnetic and fluorescent properties exhibited, the nanosystems can be considered potential candidates for cell tracking and as a platform in nanotheranostics (MRI, magnetic hyperthermia, and photodynamic therapy).

Solvothermally synthesized magnetite nanorods for application in magnetic hyperthermia and photothermia

The development of the multi-functional nanostructures has recently been of particular interest in therapeutic research for various diseases including atherosclerosis, cancer, etc. Indeed, the use of multi-responsive nanostructures that can remotely be activated by different stimuli is a promising strategy to combine the advantages of standalone methods and overcome their intrinsic drawbacks. In this regard, thermal treatment using heat-generating magnetic nanostructures that can remotely respond to a wide range of electromagnetic stimuli is of especial importance, mainly applied through magnetic hyperthermia therapy (MHT) and photothermal therapy (PTT) modalities. In this work, magnetite (Fe3O4) nanorods (MNRs) were synthesized using a one-pot solvothermal process. Adjusting the amount of hexadecylamine capping ligand and the filling percentage of the autoclave, uniformed-sized MNRs of 4·46nm in diameter and 31·09nm in length were prepared and investigated in terms of their heat-generating ability for application in the MHT and PTT. The experimental results show the good heat-generating ability of the MNRs in both modalities with the maximum absorption rate (SAR) values of 228.51 W/g (MHT) and 56.59 W/g (PTT).

Dynamical analysis of a ferrofluid subjected to oscillatory field and shear rates: Applications to magnetic hyperthermia

The dynamical magnetic response of a small sample of ferrofluid is investigated numerically. A validated in-house research code is used to compute the translational and rotational motion of the particles. This code uses a robust scheme of Ewald summation to compute long-range periodic torques and forces between the particles. The model of the ferrofluid consists in a suspension of magnetic hard spheres replicated in lattices to ensure the convergence of the system’s transport properties. Ensemble averages over several realizations for each simulation are carried out. The suspension is subjected to field and shear time-dependent excitations. The effect of magnetic hyperthermia is evaluated by the average rate of internal energy dissipation due to an oscillatory magnetic field and oscillatory shear rate. Nonlinear dynamical tools such as phase spaces and Poincaré maps are applied to interpret the dynamical behavior of the suspension. Results show that when the suspension reaches its saturation magnetization due to a delayed time-response of the particles the internal energy dissipation decreases with respect to the local applied field. The Poincaré maps reveal that in dilute regimes the system presents quasi-periodic behavior for an alternating magnetic field. Also, the application of an oscillatory shear-rate increases the bulk internal energy of the system due to the magneto-viscous effect, even though it diminishes the internal area of the hysteresis loop. This work brings a better understanding of the dynamical response of ferrofluids that could be useful in magnetic hyperthermia applications.

Alginate functionalized magnetic-silica composites for pH-responsive drug delivery and magnetic hyperthermia applications

A biopolymer sodium alginate (Alg) functionalized core–shell magnetic silica composite (FeNP@SiOH@Alg) has been proposed for pH-responsive drug delivery and magnetic hyperthermia applications. Various instruments such as XRD, FTIR, SEM, and TGA analysis were accessed to characterize the FeNP@SiOH@Alg. Under the alternating magnetic field (AMF), the magnetic hyperthermia and pH-responsive drug delivery efficiency of the prepared FeNP@SiOH@Alg were examined using doxorubicin (Dox) as a modal drug. Furthermore, the in vitro biocompatibility of the FeNP@SiOH@Alg on MDA-MB-231 cells was examined. All the findings indicated that FeNP@SiOH@Alg is effective for magnetic hyperthermia-based chemotherapy applications in cancer therapy.

Influence of Controlled Dipolar Interaction for Polymer-Coated Gd-Doped Magnetite Nanoparticles toward Magnetic Hyperthermia Application.

To maximize heat release from immobilized nanoparticles (NPs), a detailed understanding of the controlled dipolar interaction is essential for challenging magnetic hyperthermia (MH) therapies. To design optimal MH experiments, it is necessary to precisely determine magnetic states impacted by the inevitable concurrence of magnetic interactions under a common experimental form. In this work, we describe how the presence of dipolar interaction significantly alters the heating mechanism of host materials when NPs are embedded in them for MH applications. The concentration of the NPs and the intensity of their interaction can profoundly impact the amplitude and shape of the heating curves of the host material. The heating capability of interacting NPs might be enhanced or diminished, depending on their concentration within the host material. We propose chitosan- and dextran-coated Gd-doped Fe3O4 NPs directing dipole interactions effective for the linear regime to enlighten the pragmatic trends. The outcomes of our study may have substantial implications for cancer therapy and could inspire novel approaches for maximizing the effectiveness of MH.

Additive Manufacturing of Iron Carbide Incorporated Bioactive Glass Scaffolds for Bone Tissue Engineering and Drug Delivery Applications.

In this study, we have synthesized a bioactive glass with composition 45SiO2-20Na2O-23CaO-6P2O5-2.5B2O3-1ZnO-2MgO-0.5CaF2 (wt %). Further, it has been incorporated with 0.4 wt % iron carbide nanoparticles to prepare magnetic bioactive glass (MBG) with good heat generation capability for potential applications in magnetic field-assisted hyperthermia. The MBG scaffolds have been fabricated using extrusion-based additive manufacturing by mixing MBG powder with 25% Pluronic F-127 solution as the binder. The saturation magnetization of iron carbide nanoparticles in the bioactive glass matrix has been found to be 80 emu/g. The morphological analysis (pore size distribution, porosity, open pore network modeling, tortuosity, and pore interconnectivity) was done using an in-house developed methodology that revealed the suitability of the scaffolds for bone tissue engineering. The compressive strength (14.3 ± 1.6 MPa) of the MBG scaffold was within the range of trabecular bone. The in vitro test using simulated body fluid (SBF) showed the formation of apatite indicating the bioactive nature of scaffolds. Further, the drug delivery behaviors of uncoated and polycaprolactone (PCL) coated MBG scaffolds have been evaluated by loading an anticancer drug (Mitomycin C) onto the scaffolds. While the uncoated scaffold demonstrated the drug's burst release for the initial 80 h, the PCL-coated scaffold showed the gradual release of the drug. These results demonstrate the potential of the proposed MBG for bone tissue engineering and drug delivery applications.

Synthesis and characterization of magnetite coated by maltodextrin for application in magnetic hyperthermia

This study aimed to synthesize magnetite nanoparticles proposing a new core with maltodextrin using the coprecipitation method in an alkaline medium, with the potential application in magnetic hyperthermia for cancer treatment.

Ferromagnetic resonance-based heat dissipation in dumbbell-like Au–Fe3O4 nanoparticles

Ferromagnetic resonance (FMR) holds promise for heating magnetic nanoparticles (MNPs) in cancer therapy, especially for rapidly heating MNPs. This study aims to enhance the FMR-based heating efficiency of multifunctional hybrid gold and iron oxide nanoparticles (Au-Fe3O4 NPs) as theranostic agents. We experimentally investigate the FMR-based heating properties of newly developed dumbbell-like Au-Fe3O4 NPs, which feature ∼5 nm gold and 15 nm iron oxide components, in comparison to our previously developed Au-coated Fe3O4 NPs (Fe3O4 core ∼5.2 nm, Au shell thickness ∼0.5 nm). For comparison, we also synthesize pure Fe3O4 NPs (∼11 nm) under the same experimental conditions as the dumbbell-like Au-Fe3O4 NPs but without 5 nm Au seeds. Temperature measurements are taken at various DC fields (HDC = 0‒1600 Oe) under a radiofrequency (RF) field (fAC = 4 GHz, HAC = 1.265 Oe) for ∼13s. The results reveal a rapid temperature rise during RF field ON, followed by a decline upon RF field OFF. Remarkably, dumbbell-like Au-Fe3O4 NPs achieve a peak temperature increase of 23.4 °C, corresponding to a heating rate of 1.73 °C/s at HDC = 400 Oe, surpassing the combined values of ∼11 nm Fe3O4 NPs (11.0 °C, i.e., 0.83 °C/s at HDC = 1000 Oe) and ∼5 nm Au NPs (3.5 °C). Comparing these results to our previously developed Au-coated Fe3O4 NPs, which achieved a heating rate of 1.29 °C/s (temperature rise 16.9 °C) under HDC = 1200 Oe with an RF field at fAC = 4 GHz and a significantly higher HAC = 4 Oe (i.e. for HAC = 1.265 Oe, the estimated heating rate was 0.129 °C/s with a temperature rise of 1.69 °C), the dumbbell-shaped Au-Fe3O4 NPs demonstrate a substantially higher temperature increase by 13.4 times. These findings highlight the exceptional potential of dumbbell-shaped Au-Fe3O4 NPs for application in magnetic hyperthermia.

Regulation of magnetic moment and magnetic anisotropy of magnetite by doping transition metal elements

Magnetic Fe<sub>3</sub>O<sub>4</sub> nanoparticles show promising applications in nanomedicine. The saturation magnetization (<i>M</i><sub>S</sub>) and magnetic anisotropy are critical for the applications of Fe<sub>3</sub>O<sub>4</sub> nanoparticles in drug delivery and magnetic hyperthermia. Here, by density functional computation, the doping effects of 3d and 4d transition metal elements (including Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Y, Zr, Nb, Mo, Tc, Ru, Rh, Pd, Ag and Cd) on the magnetic properties of Fe<sub>3</sub>O<sub>4</sub> are investigated in-depth. A conventional cell of Fe<sub>3</sub>O<sub>4</sub>, containing 24 Fe atoms and 32 O atoms, has been used to investigate the doping of group III elements. One 3d or 4d atom is doped in one conventional cell of Fe<sub>3</sub>O<sub>4</sub>, resulting in the formation of X<sub>0.125</sub>Fe<sub>2.875</sub>O<sub>4</sub> where X represents the dopant. The results show that the doping of most 3d and 4d transition metal elements will reduce the total magnetic moment, while the doping of Ag, Zn and Cd in Fe<sub>3</sub>O<sub>4</sub> will increase the total magnetic moment by 19%–22%. However, it is hard to dope Ag into Fe<sub>3</sub>O<sub>4</sub> according to the positive formation energy. Therefore, Zn and Cd are good candidates to improve the <i>M</i><sub>S</sub> of Fe<sub>3</sub>O<sub>4</sub>. The doping of Zn and Cd has also an influence on the magnetic anisotropy of Fe<sub>3</sub>O<sub>4</sub>. For Zn<sub>0.125</sub>Fe<sub>2.875</sub>O<sub>4</sub>, the magnetic anisotropy energy is about 0.25 meV per cell, which is slightly larger than that of intrinsic Fe<sub>3</sub>O<sub>4</sub> (0.2 meV per cell). Interestingly, the doping of Cd (Cd<sub>0.125</sub>Fe<sub>2.875</sub>O<sub>4</sub>) will greatly increase the magnetic anisotropy energy to 0.8 meV per cell, which is significant for the specific absorption rate in the magnetic hyperthermia application. In addition, the doping of Zn and Cd will not induce any defect states in the band gap according to the density of states. Zn<sub>0.125</sub>Fe<sub>2.875</sub>O<sub>4</sub> and Cd<sub>0.125</sub>Fe<sub>2.875</sub>O<sub>4</sub> are both semiconducting and both the top of valence band and the bottom of conduction band originate from octahedral Fe. This is because the impurity states are very deep in energy. Our research results show that doping Cd is a feasible way to improve the performance of Fe<sub>3</sub>O<sub>4</sub> as a material for drug delivery and magnetic hyperthermia.

Injectable Thermoresponsive Microparticle/Hydrogel System with Superparamagnetic Nanoparticles for Drug Release and Magnetic Hyperthermia Applications.

Cancer is a disease that continues to greatly impact our society. Developing new and more personalized treatment options is crucial to decreasing the cancer burden. In this study, we combined magnetic polysaccharide microparticles with a Pluronic thermoresponsive hydrogel to develop a multifunctional, injectable drug delivery system (DDS) for magnetic hyperthermia applications. Gellan gum and alginate microparticles were loaded with superparamagnetic iron oxide nanoparticles (SPIONs) with and without coating. The magnetic microparticles' registered temperature increases up to 4 °C upon the application of an alternating magnetic field. These magnetic microparticles were mixed with drug-loaded microparticles, and, subsequently, this mixture was embedded within a Pluronic thermoresponsive hydrogel that is capable of being in the gel state at 37 °C. The proposed DDS was capable of slowly releasing methylene blue, used as a model drug, for up to 9 days. The developed hydrogel/microparticle system had a smaller rate of drug release compared with microparticles alone. This system proved to be a potential thermoresponsive DDS suitable for magnetic hyperthermia applications, thus enabling a synergistic treatment for cancer.