Magnetic Nanoparticle Hyperthermia Research Articles

Model predictive control (MPC) applied to a simplified model, magnetic nanoparticle hyperthermia (MNPH) treatment process

Magnetic nanoparticle hyperthermia (MNPH) has emerged as a promising cancer treatment that complements conventional ionizing radiation and chemotherapy. MNPH involves injecting iron-oxide nanoparticles into the tumor and exposing it to an alternating magnetic field (AMF). Iron oxide nanoparticles produce heat when exposed to radiofrequency AMF due to hysteresis loss. Minimizing the non-specific heating in human tissues caused by exposure to AMF is crucial. A pulse-width-modulated AMF has been shown to minimize eddy-current heating in superficial tissues. This project developed a control strategy based on a simplified mathematical model in MATLAB SIMULINK® to minimize eddy current heating while maintaining a therapeutic temperature in the tumor. A minimum tumor temperature of 43 [°C] is required for at least 30 [min] for effective hyperthermia, while maintaining the surrounding healthy tissues below 39 [°C]. A model predictive control (MPC) algorithm was used to reach the target temperature within approximately 100 [s]. As a constrained MPC approach, a maximum AMF amplitude of 36 [kA/m] and increment of 5 [kA/m/s] were applied. MPC utilized the AMF amplitude as an input and incorporated the open-loop response of the eddy current heating in its dynamic matrix. A conventional proportional integral (PI) controller was implemented and compared with the MPC performance. The results showed that MPC had a faster response (30 [s]) with minimal overshoot (1.4 [%]) than PI controller (115 [s] and 5.7 [%]) response. In addition, the MPC method performed better than the structured PI controller in its ability to handle constraints and changes in process parameters.

Influence of size, volume concentration and aggregation state on magnetic nanoparticle hyperthermia properties versus excitation conditions.

Treatment planning in magnetic hyperthermia requires a thorough knowledge of specific loss power of magnetic nanoparticles as a function of size and excitation conditions. Moreover, in biological tissues the magnetic nanoparticles can aggregate into clusters, making the evaluation of their heating performance more challenging because of the magnetostatic dipole-dipole interactions. In this paper, we present a comprehensive modelling analysis of 10-40 nm sized spherical magnetite (Fe3O4) nanoparticles, investigating how their heating properties are influenced by magnetic field parameters (peak amplitude and frequency), and by volume concentration and aggregation state. The analysis is performed by means of an in-house micromagnetic numerical model, which solves the Landau-Lifshitz-Gilbert equation under the assumption of single-domain nanoparticles, including thermal effects via a Langevin approach. The obtained results provide insight into how to tune hyperthermia properties by varying magnetic nanoparticle size, under different excitation magnetic fields fulfilling the Hergt-Dutz limit (frequency between 50 kHz and 1 MHz, and peak amplitude between 1 kA m-1 and 50 kA m-1). Special attention is finally paid to the role of volume concentration and aggregation order, putting in evidence the need for models able to account for stochasticity and clustering in spatial distribution, to accurately simulate the contribution of magnetostatic dipole-dipole interactions in real applications.

Evaluation of a Balloon Implant for Simultaneous Magnetic Nanoparticle Hyperthermia and High-Dose-Rate Brachytherapy of Brain Tumor Resection Cavities

Previous work has reported the design of a novel thermobrachytherapy (TBT) balloon implant to deliver magnetic nanoparticle (MNP) hyperthermia and high-dose-rate (HDR) brachytherapy simultaneously after brain tumor resection, thereby maximizing their synergistic effect. This paper presents an evaluation of the robustness of the balloon device, compatibility of its heat and radiation delivery components, as well as thermal and radiation dosimetry of the TBT balloon. TBT balloon devices with 1 and 3 cm diameter were evaluated when placed in an external magnetic field with a maximal strength of 8.1 kA/m at 133 kHz. The MNP solution (nanofluid) in the balloon absorbs energy, thereby generating heat, while an HDR source travels to the center of the balloon via a catheter to deliver the radiation dose. A 3D-printed human skull model was filled with brain-tissue-equivalent gel for in-phantom heating and radiation measurements around four 3 cm balloons. For the in vivo experiments, a 1 cm diameter balloon was surgically implanted in the brains of three living pigs (40–50 kg). The durability and robustness of TBT balloon implants, as well as the compatibility of their heat and radiation delivery components, were demonstrated in laboratory studies. The presence of the nanofluid, magnetic field, and heating up to 77 °C did not affect the radiation dose significantly. Thermal mapping and 2D infrared images demonstrated spherically symmetric heating in phantom as well as in brain tissue. In vivo pig experiments showed the ability to heat well-perfused brain tissue to hyperthermic levels (≥40 °C) at a 5 mm distance from the 60 °C balloon surface.

Evaluation of Magnetic Hyperthermia Efficiency of PEG-Coated Fe3O4 Nanoparticles

Magnetic nanoparticle hyperthermia has drawn considerable interest in cancer therapy. In this study, we report the synthesis of PEG-coated Fe3O4 nanoparticles and evaluate their suitability for magnetic hyperthermia applications. Fe3O4 nanoparticles were synthesized by the chemical coprecipitation method, which are coated with polyethylene glycol (PEG). PEG-coated Fe3O4 nanoparticles were characterized by X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), vibrating sample magnetometer (VSM), dynamic light scattering (DLS) and transmission electron microscopy (TEM). Synthesized nanoparticles possess inverse-spinel structural with a crystallite size of 9.1[Formula: see text]nm. From the M-H hysteresis loops, it was confirmed that the synthesized Fe3O4 nanoparticles were superparamagnetic. The physical size of bare Fe3O4 nanoparticles, as determined from the HR-TEM, is [Formula: see text][Formula: see text]nm, and the corresponding hydrodynamic size of PEG-coated Fe3O4 nanoparticles is [Formula: see text][Formula: see text]nm. Magnetic hyperthermia efficiency of PEG-coated Fe3O4 nanoparticles was determined as a function of magnetic field frequency (162–935.6[Formula: see text]kHz), field strength (5–12[Formula: see text]mT) and nanoparticle concentration (1–100[Formula: see text]mg/mL). Temperature rise in an aqueous dispersion of PEG-coated Fe3O4 nanoparticles was measured for 20[Formula: see text]min. The specific loss power (SLP) was calculated by the corrected slope method. SLP values of PEG-coated Fe3O4 nanoparticles increase with magnetic field frequency and field strength and decrease with nanoparticle concentration. The optimum hyperthermia performance of PEG-coated Fe3O4 nanoparticles was observed for 935.6[Formula: see text]kHz frequency, 10[Formula: see text]mT field strength and 25[Formula: see text]mg/mL concentration. Under these conditions, the measured SLP of PEG-coated Fe3O4 nanoparticles was 4.43[Formula: see text]W/g. These results show that the synthesized PEG-coated Fe3O4 nanoparticles could be a potential candidate for magnetic hyperthermia treatment of cancer.

Tumor size dependent MNP dose evaluation in realistic breast tumor models for effective magnetic hyperthermia

The goal of the current investigation is to determine the breast tumor size-dependent MNP (Magnetic nano-particle) dose (mg/cm3) that can induce the required therapeutic effects during magnetic nanoparticle hyperthermia (MNH). The investigation is done through the MNH simulations on the tumor models generated from DCE_MRI DICOM images of breast cancer from TCIA (‘The Cancer Imaging Archive’). Five tumor models are created from MRI data using 3D slicer software having size range of 3 cm3 to 15 cm3. The FEM-based solver (COMSOL multi-physics) is used to simulate bioheat transfer physics in all five extracted models. Single and multi-point injection strategies have been adopted to induce MNP in tumor tissues. The required MNP dose that may induce necessary therapeutic effects is evaluated by comparing the therapeutic effects produced by constant dose (CD) (5 mg/cm3) and variable reduced dose (RD) (5.5–2.8 mg/cm3) methodologies. Results show that for the requisite therapeutic effects, injected MNP doses (mg/cm3) should not remain constant as the size of the tumor increases. In fact, MNP dose (mg/cm3) should be reduced as the size of the tumor increases. Results also show that RD works better with a multi-injection strategy than a single injection of MNP. It has been found that the effective MNP dose (mg/cm3) is reduced by 50 % for the biggest tumor size (15 cm3) using multi-injection MNP delivery with respect to the smallest tumor (3 cm3) selected in this study.

Nanowarming improves survival of vitrified ovarian tissue and follicular development in a sheep model

Tissue cryopreservation has allowed long term banking of biomaterials in medicine. Ovarian tissue cryopreservation in particular helps patients by extending their fertility window. However, protection against tissue injury during the thawing process has proven to be challenging. This is mainly due to the heterogenous and slow distribution of the thermal energy across the vitrified tissue during a conventional warming process. Nanowarming is a technique that utilizes hyperthermia of magnetic nanoparticles to accelerate this process. Herein, hyperthermia of synthesized PEGylated silica-coated iron oxide nanoparticles was used to deter the injury of cryopreserved ovarian tissue in a sheep model. When compared to the conventional technique, our findings suggest that follicular development and gene expression in tissues warmed by the proposed technique have been improved. In addition, Nanowarming prevented cellular apoptosis and oxidative stress. We therefore conclude that Nanowarming is a potential complementary candidate to increase efficiency in the ovarian cryopreservation field.

In-silico investigation of intratumoural magnetic hyperthermia for breast cancer therapy using FePt or FeCrNbB magnetic nanoparticles

In this work, we conduct a numerical study on magnetic nanoparticle hyperthermia for the treatment of a breast tumour. The geometry of the problem is comprised of a deformed ellipsoidal tumour region, a healthy glandular tissue region, a fat tissue layer and a skin tissue layer. An aqueous suspension of magnetic nanoparticles (FeCrNbB or FePt) is directly injected into the breast tumour using a syringe. The perfusion of blood through the tissue regions is modelled using the Darcy-Brinkman-Forchheimer equation, and the shear-thinning behaviour of blood is described by the Carreau–Yasuda model. The transport and deposition of nanoparticles within the tissues, the temperature distribution during therapy, and the survival rates of healthy cells and cancer cells are also considered. The governing equations with their associated initial and boundary conditions are solved using the finite element method, and the solution algorithm developed in FreeFEM++ was validated against results from the existing literature. Subsequently, the influence of the nanoparticle solid volume fraction, injection time, and magnetic field amplitude and oscillation frequency on the velocity, temperature, nanoparticle concentration distribution, duration required for effective hyperthermia, and thermal damage to healthy tissues was examined. The numerical results reveal that the cell damage is greater in skin tissue than the healthy gland and fat tissues. For small injection time (tinj=0.4), the healthy gland tissue damage is greater for FePt nanoparticles than FeCrNbB nanoparticles. However, this trend is reversed for larger injection times (tinj=0.5, 0.6). For small magnetic field frequency (ω=5×104, 105), the maximum tissue temperature is higher with FePt nanoparticles than FeCrNbB nanoparticles, but a reversal in trend occurs for larger values of ω (ω=2×105). The findings show that the time duration required for effective magnetic hyperthermia and thermal damage to the healthy tissue regions is reduced with increased injected nanoparticle volume fraction, duration of nanoparticle injection, and the amplitude and frequency of the alternating magnetic field. Moreover, the effective hyperthermia duration and the healthy tissue damage are less for FePt nanoparticles than FeCrNbB nanoparticles.

E. coli Phagelysate: A Primer to Enhance Nanoparticles and Drug Deliveries in Tumor

The tumor microenvironment (TME), where cancer cells reside, plays a crucial role in cancer progression and metastasis. It maintains an immunosuppressive state in many tumors and regulates the differentiation of precursor monocytes into M1 (anti-tumor)- and M2 (pro-tumor)-polarized macrophages, and greatly reduces anticancer drug and nanoparticle delivery. As a result, the effectiveness of recently developed chemo- and/or nanotechnology-mediated immune and magnetic nanoparticle hyperthermia (mNPH) therapies is inhibited significantly. One of the ways to overcome this limitation is to use E. coli phagelysate as a primer to modify the tumor microenvironment by switching tumor-associated M2 macrophages to anti-tumor M1 macrophages, and initiate the infiltration of tumor-associated macrophages (TAMs). Recently, bacteriophages and phage-induced lysed bacteria (bacterial phagelysates—BPLs) have been shown to be capable of modifying the tumor-associated environment. Phage/BPL-coated proteins tend to elicit strong anti-tumor responses from the innate immune system, prompting phagocytosis and cytokine release. It has also been reported that the microenvironments of bacteriophage- and BPL-treated tumors facilitate the conversion of M2-polarized TAMS to a more M1-polarized (tumoricidal) environment post-phage treatment. This paper demonstrates the feasibility and enhanced efficacy of combining E. coli phagelysate (EcPHL) and mNPH, a promising technology for treating cancers, in a rodent model. Specifically, we illustrate the EcPHL vaccination effect on the TME and mNP distribution in Ehrlich adenocarcinoma tumors by providing the tumor growth dynamics and histology (H&E and Prussian blue) distribution of mNP in tumor and normal tissue.

FEM thermal assessment of a 3-D irregular tumor with capillaries in magnetic nanoparticle hyperthermia via dissimilar injection points

In this study, simulation of magnetic nanoparticle hyperthermia is performed on a 3D tumor model constructed based on a CT image of a tumor. In the first step, magnetic nanoparticles are injected into two points of the tumor tissue with the same parameters. Results show that temperature profiles in the vicinity of the injection points are not similar due to the presence of blood capillaries. Therefore, the effects of using dissimilar injection parameters for the two injection points on the heating pattern and damage fraction of the tumor are investigated. The results demonstrate that using dissimilar values for injection parameters such as injection rate, injection time, and nanofluid volume fraction is a way to achieve a higher damage fraction of the tumor cells, but, the asynchronous injections strategy does not lead to more significant damage to the tumor. None of the cases showed significant improvement in the uniformity of the temperature distribution, suggesting that conducting injections under the same conditions is the best way to create an almost uniform temperature profile. The numerical simulation validation results also advocate the accuracy of the model used in this study. This research can serve as a guide for designing parameters for future studies.

Design and Assessment of a Novel Biconical Human-Sized Alternating Magnetic Field Coil for MNP Hyperthermia Treatment of Deep-Seated Cancer.

Magnetic nanoparticle (MNP) hyperthermia therapy is a treatment technique that can be used alone or as an adjunct to radiation and/or chemotherapies for killing cancer cells. During treatment, MNPs absorb a part of electromagnetic field (EMF) energy and generate localized heat when subjected to an alternating magnetic field (AMF). The MNP-absorbed EMF energy, which is characterized by a specific absorption rate (SAR), is directly proportional to AMF frequency and the magnitude of transmitting currents in the coil. Furthermore, the AMF penetrates inside tissue and induces eddy currents in electrically conducting tissues, which are proportional to the electric field (J = σE). The eddy currents produce Joule heating (<J·E> = 0.5·σ·E2) in the normal tissue, the rate of energy transfer to the charge carriers from the applied electric fields. This Joule heating contains only the electric field because the magnetic field is always perpendicular to the velocity of the conduction charges, i.e., it does not produce work on moving charge. Like the SAR due to MNP, the electric field produced by the AMF coil is directly proportional to AMF frequency and the magnitude of transmitting currents in the coil. As a result, the Joule heating is directly proportional to the square of the frequency and transmitter current magnitude. Due to the fast decay of magnetic fields from an AMF coil over distance, MNP hyperthermia treatment of deep-seated tumors requires high-magnitude transmitting currents in the coil for clinically achievable MNP distributions in the tumor. This inevitably produces significant Joule heating in the normal tissue and becomes more complicated for a standard MNP hyperthermia approach for deep-seated tumors, such as pancreatic, prostate, liver, lung, ovarian, kidney, and colorectal cancers. This paper presents a novel human-sized AMF coil and MNP hyperthermia system design for safely and effectively treating deep-seated cancers. The proposed design utilizes the spatial distribution of electric and magnetic fields of circular coils. Namely, it first minimizes the SAR due to eddy currents in the normal tissue by moving the conductors away from the tissue (i.e., increasing coils' radii), and second, it increases the magnetic field at the targeted area (z = 0) due to elevated coils (|z| > 0) by increasing the radius of the elevated coils (|z| > 0). This approach is a promising alternative aimed at overcoming the limitation of standard MNP hyperthermia for deep-seated cancers by taking advantage of the transmitter coil's electric and magnetic field distributions in the human body for maximizing AMF in tumor regions and avoiding damage to normal tissue. The human-sized coil's AMF, MNP activation, and eddy current distribution characteristics are investigated for safe and effective treatment of deep-seated tumors using numerical models. Namely, computational results such as AMF, Joule heating SAR, and temperature distributions are presented for a full-body, 3D human model. The SAR and temperature distributions clearly show that the proposed human-sized AMF coil can provide clinically relevant AMF to the region occupied by deep-seated cancers for the application of MNP hyperthermia therapy while causing less Joule heating in the normal tissues than commonly used AMF techniques.

Effects of injection rates and tissue diffusivity in magnetic nano-particle hyperthermia.

Effects of injection rate and tumor physiology on the diffusion of magnetic nano-particles (MNPs) and temperature profile during magnetic hyperthermia are investigated in this work. The study considers three injection rates (2.5 μL/min, 10 μL/min, and 40 μL/min), and two MNP diffusion coefficients (10-9 m2/s and 10-11 m2/s). The simulation of this physics has been done on 3D tumor surrounded by healthy tissue. Transient MNP distribution in tissue is evaluated using Darcy's flow model and the MNP transport (convection-diffusion) equation. The temperature profile in the tumor model is computed by solving Penne's bioheat transfer equation (PBHTE). Results show tumors with high collagen content (with low MNP diffusivity) are more restrictive towards MNP transport than tumors having low collagen content. Thus, tumors with low MNP diffusivity need a higher injection rate to increase the homogeneity of MNP concentration as well as temperature profile during thermo-therapy. Results also show that, MNP fluid injected with a higher injection rate produces a more uniform MNP concentration up to greater depth than the lower injection rate.

The SLP estimation of the nanoparticle systems using size-dependent magnetic properties for the magnetic hyperthermia therapy

Magnetic Nanoparticle hyperthermia (MNH) is one of the hyperthermia therapy in which temperature gain is achieved through magnetic nanoparticles in the tumor tissue/targeted region. The key parameters for efficient heating in MNH are magnetic nanoparticle (MNPs) properties, its size & materials, and magnetic field parameters (amplitude and frequency). Thus, the present study investigates the effects of these parameters on heat generation during MNH. In this study, a comparison of heat generation by three nanoparticle systems (CoFe2O4, Fe3O4, and MnFe2O4) and its dependency on size & magnetic field parameters is theoretically investigated. The quantification of specific loss power (SLP) of nanoparticle systems depending on its size-dependent saturation magnetization (MS) and the anisotropy constant (Keff). of nanoparticles has been done in this work. Correlations for MS and Keff based on the previously reported experimental data have been established for considered MNP systems. The comparisons show that SLP estimation using MNP size-dependent saturation magnetization (MS) (Fig. 4) are closer to the experimentally reported values of SLP for all considered MNP systems (CoFe2O4, Fe3O4, MnFe2O4) in comparison to SLP estimated by fixed values of saturation magnetization (MS) and anisotropy constant (Keff). Results show that dissipated power reaches a peak at a certain particle size (DO). However, the (DO) varies with the magnetic field frequency and amplitude. It decreases as the frequency increases at a particular field amplitude. In addition, the SLP increment ceases after a certain frequency (fO) that is around 500 kHz for considered MNP systems. On the other hand, the SLP continuously increases with an increase in field amplitude. Thus this work incorporates the empirical correlations as well as experimental data to predict the SLP for three magnetic nanoparticle systems generally utilized in the MNH.

Numerical modelling of magnetic nanoparticle behavior in an alternating magnetic field based on multiphysics coupling

In magnetic nanoparticle hyperthermia, the magnetic nanoparticles (MNPs) start oscillations when they are exposed to an alternating magnetic field, which may generate ultrasound waves. These resulting oscillations of nanoparticles can lead to the movement of drug carrier liposomes. In this study, a multiphysics coupling model of magnetic nanoparticle behavior in an alternating magnetic field was developed, implementing solid mechanics compliance parameters and piezomagnetic coupling matrices. A detailed sensitivity study was conducted to examine the effects of size and elastic modulus of MNPs, distribution and distance between two MNPs, elasticity and viscosity of the glycerol medium and mesh element sizes on the output displacement signals of MNPs. The results indicated that magnetic nanoparticles undergo some displacements when they are exposed to an alternating magnetic field. These oscillations may generate ultrasound waves, though the amount of displacement for each nanoparticle is negligibly small. It is expected that aggregated nanoparticles result in much higher oscillations.

PHSOR03 Presentation Time: 12:40 PM: Radiation Dosimetry of a Dual-Modality Balloon Implant for Simultaneous HDR Brachytherapy and Magnetic Nanoparticle Hyperthermia to Treat Brain Tumor Resection Cavities

<h3>Purpose</h3> Glioblastoma multiforme (GBM) is an aggressive brain tumor that generally recurs locally and has a dismal median survival of less than 18 months<i>. In vivo</i> studies have shown that simultaneous hyperthermia and radiation can enhance the radiation response by a factor of up to 5. Our group developed a novel dual-modality thermobrachytherapy (TBT) balloon device to accomplish this goal. The balloon will combine magnetic fluid hyperthermia and HDR brachytherapy, which will be delivered right after brain tumor resection, so that the at-risk tissue adjacent to the tumor resection cavity will conform to the balloon shape and receive uniform radiation and thermal dose. This abstract focuses on the possible effects of hyperthermia on radiation dosimetry as well as the effects of balloon shape. <h3>Methods</h3> The current version of our TBT balloon device consists of a balloon filled with magnetic nanoparticle solution (nanofluid) and a flexible sheath with three ports to insert the HDR catheter and fiber-optic thermal probe and inject the nanofluid. We tested the balloon in air and activated the nanofluid using an external magnetic field induced by a 133 kHz induction coil. Two balloon designs were tested: a spherical one with 4 cm diameter, and a teardrop-shaped balloon with an axial diameter of 3 cm and measuring 3.7 cm along the shaft. We used Gafchromic film and RIT imaging software to analyze the in-air dose distribution of an HDR source dwell in both types of balloons, filled with distilled water and then nanofluid, as well as without and with simultaneous hyperthermia, where the coil power was escalated until reaching intra-balloon temperatures greater than 55°C. Experimental setup and radiation dose profiles can be found in Figure 1. <h3>Results</h3> The presence of the nanofluid, magnetic field and heat up to 66°C did not affect radiation dose distribution significantly in the spherical balloon (less than 10% difference). However, the teardrop-shaped balloon dose profiles showed a notable difference (about 20%) in dose magnitude with the presence of nanofluid and/or heat. Nonetheless dose distributions looked symmetrical in all cases. <h3>Conclusions</h3> The current device design is still in progress, but this study illustrated that a spherical balloon shape may be preferential for simultaneous hyperthermia and HDR brachytherapy. Furthermore, this radiation dosimetry study demonstrated compatibility and robustness of the prototype balloon components and desirable symmetrical dose distribution.

Tailored cancer therapy by magnetic nanoparticle hyperthermia: A virtual scenario simulation method

Background and objectiveHyperthermia is a cancer treatment aiming to induce cell death by directly warming cancerous tissues above 40 °C. This technique can be applied both individually and together with other cancer therapies. The main challenge for researchers and medics is to heat only tumoral cells avoiding global or localized heating of sane tissues. The objective in this study is to provide a realistic virtual scenario to develop an optimized multi-site injection plan for tailored magnetic nanoparticle-mediated hyperthermia applications. MethodsA three-dimensional model of a cat's back was tested in three different simulation scenarios, showing the impact of magnetic nanoparticles in each specific environment configuration. ResultsAs a result of this study. This simulation method can, minimising the affection to healthy tissue. ConclusionsThis virtual method will help real and personalized therapy planning and tailor the dose and distribution of magnetic nanoparticles for an enhanced hyperthermia cancer treatment.

Simulation of heat transfer, mass transfer and tissue damage in magnetic nanoparticle hyperthermia with blood vessels

Numerical simulation of magnetic nanoparticle hyperthermia for cancer treatment has been investigated in this study. The presented simulation did account for the effects of fluid flow, mass flow, and heat transfer during the MNP hyperthermia. The tumor was assumed to be a porous slab, 30% of which had been necrosed previously, with two capillaries, where magnetic nanoparticles were added into the bloodstream and distributed in the tumor by blood flow through capillaries. Fluid flow, mass transfer by capillaries, and interstitial tissues have been coupled in this study. Furthermore, tumor tissue damage has been calculated using a thermal damage indicator. The goal of this research is to find an optimum injection duration and exposure time in order to maximize hyperthermia treatment effectiveness using the BOBYQA optimization method. At the end of the 1-h time hyperthermia treatment, most of the non-necrotic tissue of the tumor were damaged. Moreover, the fraction of damaged tissue increased to more than 90% in some parts of the tumor. Results of this study indicate that MNP hyperthermia with the proposed setup can effectively damage the tumor in just one session, making it more susceptible to complementary therapies such as radiotherapy or chemotherapy.

The role of Co2+ cation addition in enhancing the AC heat induction power of (CoxMn1–x)Fe2O4 superparamagnetic nanoparticles

The physical role of magnetically semi-hard Co2+ cation addition in enhancing the AC heat induction temperature (T AC) or specific loss power (SLP) of solid (Co x Mn1−x )Fe2O4 superparamagnetic iron oxide nanoparticles (SPIONPs) was systematically investigated at the biologically safe and physiologically tolerable range of H AC (H AC,safe = 1.12 × 109 A m−1 s−1, f appl = 100 kHz, H appl = 140 Oe (11.2 A m−1)) to demonstrate which physical parameter would be the most critical and dominant in enhancing the T AC (SLP) of SPIONPs. According to the experimentally and theoretically analyzed results, it was clearly demonstrated that the enhancement of magnetic anisotropy (K u )-dependent AC magnetic softness including the Néel relaxation time constant τ N (≈τ eff , effective relaxation time constant), and its dependent out-of-phase magnetic susceptibility primarily caused by the Co2+ cation addition is the most dominant parameter to enhance the T AC (SLP). This clarified result strongly suggests that the development of new design and synthesis methods enabling to significantly enhance the K u by improving the crystalline anisotropy, shape anisotropy, stress (magnetoelastic) anisotropy, thermally-induced anisotropy, and exchange anisotropy is the most critical to enhance the T AC (SLP) of SPIONPs at the H AC,safe (particularly at the lower f appl < 120 kHz) for clinically safe magnetic nanoparticle hyperthermia.

Computational investigation of the tumor position and ambient conditions on magnetic nanoparticle thermo-therapy

• Estimation of effects of tumor position beneath the skin on magnetic nanoparticle hyperthermia (MNPH). • Estimation of effects of therapeutic environmental conditions on MNPH. • Quantification of thermal damage in tumor as well healthy tissues in diverse therapeutic environmental conditions. • Estimation of the critical depth of the tumor up to which the variations in the therapeutic effects of MNPH are significant. The present study elucidate the effects of tumor position and clinical environmental conditions on the therapeutic effects of magnetic nanoparticle hyperthermia (MNH) in superficial like breast tumor tissue. Effects of these two factors are investigated through a three-dimensional (3D) tumor model. The position of the tumor tissue (of size 1.5 cm) within the 3D model as well as the heat transfer rate through the skin is altered to evaluate their effects on MNH. Six different positions of tumor ranging from zero-depth to the tumor depth of 1.5 times the tumor size from the skin are considered. Similarly, three different heat transfer coefficients ( h c = 2.5, 5.5, 7.5 W / m 2 K ) on the skin during thermotherapy are considered to simulate a wide range of clinical environmental conditions. MNH is induced for 1 hour using two different heating powers (with amplitudes of 10 k A / m and 12.5 k A / m at 130 k H z ) to evaluate the thermal damage (Arrhenius ( Ω =4.6) and cumulative equivalent minutes C E M 43 60 in the tissue. Results show that there exists a critical depth, which is nearly half of the tumor size, up to which the MNH is influenced by the position of the tumor. Similarly, the effects of the ambient conditions during this thermotherapy on thermal dosimetry, also cease beyond this critical depth. The estimation of the critical depth of the tumor will help in predicting the therapeutic effects of magnetic hyperthermia applicators for specifically positioned tumors in actual environmental conditions.

A mathematical model of intratumoral infusion, particle distribution and heat transfer in cancer tumors: In-silico investigation of magnetic nanoparticle hyperthermia

Tumor cells can be killed by rising the tumor temperature above 42 °C and keeping it for sufficiently longer durations by exploiting magnetic nanoparticles and alternative magnetic fields, which is known as magnetic nanoparticle hyperthermia. In-vivo experiments are often complex and difficult to perform to evaluate therapeutic efficacy. Hence, mathematical models and computer simulations are widely used as methods of investigation. Although different aspects of the treatment modality have been covered in the literature, a comprehensive model to consider the infusion of nanoparticles into the tumor, diffusion and distribution of the particles followed by heat transfer analysis to predict temperature elevation are lacking. This study presents a mathematical model to simulate clinical procedure by addressing the injection process, post-injection distribution and bio-heat transfer in the tumors considering in-vivo physiological aspects such as tumor heterogeneity and transvascular transport. The proposed model is implemented in COMSOL Multiphysics software to predict the fluid flow, particle distribution and temperature elevation in the tumor. Interstitial fluid flow is solved and utilized in predicting particle distribution through a convection-diffusion model. The obtained concentration profiles were used to calculate the nanoparticle heat generation in the tissues under an alternating magnetic field and the corresponding temperature distribution was predicted. The results demonstrate that the smaller particles diffuse faster and result in a higher temperature rise in the tumors. The numerical simulations also indicate that the ideal case of confined uniform distribution of nanoparticles inside the tumor only leads to the inaccurate prediction of the tumor temperatures and the efficiency of the treatment. In addition, it is observed that single-site injection at the tumor center does not achieve a therapeutic temperature in the entire tumor. This indicates that alternative techniques or multiple-site injections need to be investigated to achieve a therapeutic effect in large tumors.

In-silico investigation of magnetic nanoparticle hyperthermia treatment to estimate the power density and concentration required to achieve the therapeutic effect

Magnetic fluid hyperthermia elevates the tumor temperature through selective heating to eradicate tumors. To evaluate treatment efficacy, in-vitro and animal in-vivo experimental investigations are often complex and ethical constraints are major issues. With the advent of computers and computational techniques, detailed investigations of hyperthermia treatment have been practicable. The effectiveness of the treatment is associated with the temperature elevation achieved during the treatment, which directly depends on the heat generated by the magnetic particles. The present study focuses on estimating the power density required to achieve the defined therapeutic temperatures in the tumor, which is a factor in deciding the nanoparticle dosage and delivery technique. A mathematical model is presented to estimate the power density requirement in a realistic breast geometry with a tumor to replicate the in-situ clinical scenario. This study investigates the effect of required therapeutic temperature, necrotic core, tumor size, and surrounding tissue in which the tumor is present. The results show that the therapeutic temperature and power density are directly proportional while tumor size and power density are inversely related. The presence of a necrotic core reduces the power density requirements and a tumor in highly perfused tissues demands higher power densities.