Magnetic Nanoparticle Hyperthermia Research Articles

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.

Simulating Evaluation Method on Heating Performances of Magnetic Nanoparticles with Temperature-Dependent Heating Efficiencies in Tumor Hyperthermia

The magnetic nanoparticles (MNPs) with decreasing heating efficiency (characterized by specific loss power, SLP) with temperature increase, especially around the Curie temperature (TC), are expected to realize the self-regulated temperature hyperthermia of the tumor. However, the actual decrease of the SLP is gradual, resulting in the deviation of self-regulated temperatures from the measured TC. So far, no method is available for evaluating the heating performances of those MNPs. Here, by simulating the temperature-dependent SLP, the heating performances of MNPs are evaluated from three clinically concerning aspects: the capacity for effective heating, the temperature uniformity in the tumor, and the temperature stability under environmental changes such as MNP loss or tumor progression. The developed methods were applied to ZnCoCrFeO, Fe3O4, and γ-Fe2O3 MNPs. It was found that the uniform temperature distribution relies on lowering the heating power in the inner regions of the tumor, and the stable control of temperature depends on the dynamic adaptation of the heating power to the tumor temperature change. The proposed method may be used to predict the heating ability of MNPs and help the selection of MNPs for hyperthermia.

Parameterizing the Effects of Tumor Shape in Magnetic Nanoparticle Thermotherapy Through a Computational Approach

Abstract In this work, effects of tumor shape on magnetic nanoparticle hyperthermia (MNPH) are investigated and evaluated using four categories (spherical, oblate, prolate, and egg-shape) of tumor models having different morphologies. These tumors have equal volume; however, due to the differences in their shapes, they have different surface areas. The shape of tumors is quantified in terms of shape factor (ζ). Simulations for MNPH are done on the physical model constituting tumor tissue enclosed within the healthy tissue. Magnetic hyperthermia is applied (frequency 150 kHz, and magnetic field amplitude 20.5 kA/m) to all tumor models, for 1 h, after injection of magnetic nanoparticles (MNPs) at the respective tumor centroids. The distribution of MNPs after injection is considered Gaussian. The governing model (Pennes' bioheat model) of heat transfer in biological media is solved with the finite volume-immersed boundary (FV-IB) method to simulate MNPH. Therapeutic effects are calculated using the Arrhenius tissue damage model, cumulative equivalent minutes at 43 °C (CEM 43), and heterogeneity in temperature profiles of the tumors. Results show that the therapeutic effects of MNPH depend significantly on the shape of a tumor. Tumors with higher shape factors receive less therapeutic effects in comparison to the tumors having lower shape factors. An empirical thermal damage model is also developed to assess the MNPH efficacy in real complex-shaped tumors.

Design of monodispersed PVP functionalized biocompatible manganese ferrite nanoparticles for hyperthermia application

Magnetic nanoparticles which can be triggered externally by an alternating current magnetic field (AMF) have shown their potential for various biomedical applications. Magnetic hyperthermia using magnetic nanoparticles (MNPs) has emerged as a promising treatment for cancer. For effective administration of MNPs in hyperthermia, they need to show high heating attributes under physiological safe values of the field, frequency, and for a minimal amount of material. In this regard, an attempt has been made to synthesize MnFe2O4 nanoparticles and functionalize them with the biocompatible polyvinylpyrrolidone (PVP) polymer. Functionalized nanoparticles are characterized for magneto-structural and morphological analysis. The heating capacity of MNPs is contemplated to evaluate the attainability to use in hyperthermia applications. Results demonstrate that MNPs exhibited superparamagnetism with high magnetization at room temperature. Maximum specific absorption rate (SAR) 468.37 W g−1 has been observed at 335.2 Oe (and frequency 265 kHz) for PVP coated nanoparticles for 5 mg mL−1 concentration. Cell viability of PVP functionalized nanoparticles performed using the L929 cell line showed that the nanoparticles are biocompatible. The PVP-functionalized MnFe2O4 nanoparticles synthesized by the one-pot polyol method can be used as a heating mediator in magnetic hyperthermia therapy.

Two-phase model of intravenous magnetic nanoparticle hyperthermia in muscle and prostate tumours

In this work, we investigate heat transfer phenomena in muscle and prostate tissues during magnetic hyperthermia cancer therapy with intravenously-injected maghemite nanoparticles. The resulting suspension of nanoparticles in blood is considered to be a non-Newtonian nanofluid, and a two-phase model that considers Brownian and thermophoretic effects is considered. The geometrical domain is comprised of a blood vessel region, cancerous and non-cancerous (prostate or muscle) tissue regions, and a region of fat tissue. The mixed finite element technique is utilized for solving the governing equations and their associated initial and boundary conditions; triangular quadratic elements are chosen for the temperature, velocity and nanoparticle volume fraction approximations, whereas triangular linear elements are selected for the pressure approximation. Based on this numerical solution, we examine the impact of the nanoparticle volume fraction at the inlet of the blood and magnetic field oscillation frequency on heat transfer and nanoparticle transport. The findings of this study indicate that in the prostate and muscle tissue cases, the nanoparticle distribution non-uniformity and the tissue and blood vessel temperatures are increased, and the average pressure is reduced, by increasing the inlet nanoparticle concentration and magnetic field oscillation frequency. In the muscle tissue case, the mean flow velocity can be increased by increasing the inlet nanoparticle concentration and decreasing the magnetic field oscillation frequency. Based on these findings, recommendations are made for improving the effectiveness of magnetic nanoparticle hyperthermia in cancerous muscle and prostate tissues. The research conducted in this work is motivated by the need for a better understanding of the factors impacting nanoparticle transport in tissues and heat generation during magnetic hyperthermia. Using the mathematical model developed herein, tissue temperatures attained under intravenous magnetic hyperthermia treatment can be accurately predicted.

STUDIES ON THE HEATING ABILITY BY VARYING THE SIZE OF Fe3O4 MAGNETIC NANOPARTICLES FOR HYPERTHERMIA

STUDIES ON THE HEATING ABILITY BY VARYING THE SIZE OF Fe3O4 MAGNETIC NANOPARTICLES FOR HYPERTHERMIA

New Prospects in Neutering Male Animals Using Magnetic Nanoparticle Hyperthermia.

Controlling populations of free-roaming dogs and cats poses a huge challenge worldwide. Non-surgical neutering strategies for male animals have been long pursued, but the implementation of the procedures developed has remained limited to date. As submitting the testes to high temperatures impairs spermatogenesis, the present study investigated localized application of magnetic nanoparticle hyperthermia (MNH) to the testicles as a potential non-surgical sterilization method for animals. An intratesticular injection of a magnetic fluid composed of manganese-ferrite nanoparticles functionalized with citrate was administered followed by testicle exposure to an alternate magnetic field to generate localized heat. Testicular MNH was highly effective, causing progressive seminiferous tubule degeneration followed by substitution of the parenchyma with stromal tissue and gonadal atrophy, suggesting an irreversible process with few side effects to general animal health.

Breast Cancer – Diagnosis and Treatment Prolonging Life: A Review

Breast cancer is a malignant tumour that starts either in the ducts or lobules, this can be generally differentiated as either in situ or invasive (in filtering) type. It is expected that in 2014 every 1 in 8 women are likely to develop invasive breast cancer during their lifetime when compared to a decade back where an average of 1 in 10 was seen. With this increase, breast cancer alone, roughly accounts for 25 to 30% of new cancer cases this year. Despite such diagnostic statistics, there are millions of survivors across the globe and this increasing rate can be attributed to the tremendous increase in advances in treatment and also early diagnosis. New drug delivery carriers like nanoparticles, liposomes, monoclonal antibodies, etc. are being used to improve the efficacy of therapy and for site specific delivery to reduce side effects. As a result of the constant effort by researchers, today the commercial market has a range of products apart from the conventional dosage forms like Herceptin (trastuzumab), a monoclonal antibody; the others in this class are Pertuzumab (Perjeta), Kadcyla (ado-trastuzumab emtansine) used for targeted delivery; Myocet (doxorubicin), a liposomal formulation and Paclitaxel nanoparticles all these are available as injections via intravenous route or infusion in few cases. There are yet certain other promising technologies like magnetic nanoparticle hyperthermia and cMethDNA assay a very assuring method to monitor recurrence of breast cancer by a simple blood test. This review will focus on the description of disease, diagnosis, current treatment therapies and ongoing research to provide better facilities.

Numerical Investigation of Ferrofluid Preparation during In-Vitro Culture of Cancer Therapy for Magnetic Nanoparticle Hyperthermia.

Recently, in-vitro studies of magnetic nanoparticle (MNP) hyperthermia have attracted significant attention because of the severity of this cancer therapy for in-vivo culture. Accurate temperature evaluation is one of the key challenges of MNP hyperthermia. Hence, numerical studies play a crucial role in evaluating the thermal behavior of ferrofluids. As a result, the optimum therapeutic conditions can be achieved. The presented research work aims to develop a comprehensive numerical model that directly correlates the MNP hyperthermia parameters to the thermal response of the in-vitro model using optimization through linear response theory (LRT). For that purpose, the ferrofluid solution is evaluated based on various parameters, and the temperature distribution of the system is estimated in space and time. Consequently, the optimum conditions for the ferrofluid preparation are estimated based on experimental and mathematical findings. The reliability of the presented model is evaluated via the correlation analysis between magnetic and calorimetric methods for the specific loss power (SLP) and intrinsic loss power (ILP) calculations. Besides, the presented numerical model is verified with our experimental setup. In summary, the proposed model offers a novel approach to investigate the thermal diffusion of a non-adiabatic ferrofluid sample intended for MNP hyperthermia in cancer treatment.

Influence of Ca doping on ZnFe2O4 nanoparticles magnetic hyperthermia and cytotoxicity study

The biocompatibility nature of the synthesized nanoparticles (NPs) has exposed a superparamagnetic (SP) behavior with best saturation mass magnetization (Ms) values and monodispersed behavior. All these characteristics are essential, for their importance as nanomedicine in the magnetic hyperthermia (MH) treatment of cancer. The prepared powder samples were validated as capable MH mediators by their heating efficiency as measured by specific absorption rate (SAR) in calorimetric measurements. Three Ca2+ - substituted ZnFe2O4 NPs with different Ca2+ contents, the particle size, and crystallite size of the samples have been prepared. These ideal premises have permitted the investigation of the induction heating aptitudes wholly on the origin of the various chemical compositions. Enhanced magnetic features of prepared NPs initiated us to investigate these systems as capable MH agents. FT-IR spectra confirm that the presence of functional groups and vibrational modes of spinel structure. Composition information of the prepared NPs has been studied by X-ray photoelectron spectroscopy (XPS). The prepared samples have significant Ms values at 15 K (< 80 emu/g). The enhance in the Ca2+ concentration up to x = 0.5 in the structure (sample) has resulted in an enhancement of the Ms at 15 K. The SAR value for the x = 0.5 sample (1 mg/mL) is nearly 6 times greater than that of the x = 0.1 (1 mg/mL) sample. Induction heating profile measurements reveal that the heating efficiency enhances with the enhancing of the ferrofluid concentration. The outcomes obtained in this current work deliver a deep and expressive understanding of the use of prepared NPs for MH cure and pave the route for using such kinds of NPs for upcoming clinical and biomedical applications. In vitro, Prestoblue® assay test analysis from skin fibroblast confirmed the synthesized NPs were biocompatible over 0–1000 μg/mL concentrations. Based on these characterizations suggested that the prepared NPs may be significant potential agents for MH application.

A Perspective on Modelling Metallic Magnetic Nanoparticles in Biomedicine: From Monometals to Nanoalloys and Ligand-Protected Particles.

The focus of this review is on the physical and magnetic properties that are related to the efficiency of monometallic magnetic nanoparticles used in biomedical applications, such as magnetic resonance imaging (MRI) or magnetic nanoparticle hyperthermia, and how to model these by theoretical methods, where the discussion is based on the example of cobalt nanoparticles. Different simulation systems (cluster, extended slab, and nanoparticle models) are critically appraised for their efficacy in the determination of reactivity, magnetic behaviour, and ligand-induced modifications of relevant properties. Simulations of the effects of nanoscale alloying with other metallic phases are also briefly reviewed.

Cubic Nanoparticles for Magnetic Hyperthermia: Process Optimization and Potential Industrial Implementation.

Cubic nanoparticles are referred to as the best shaped particles for magnetic hyperthermia applications. In this work, the best set of values for obtaining optimized shape and size of magnetic particles (namely: reagents quantities and proportions, type of solvents, temperature, etc.) is determined. A full industrial implementation study is also performed, including production system design and technical and economic viability.

Quantitative evaluation of effects of coupled temperature elevation, thermal damage, and enlarged porosity on nanoparticle migration in tumors during magnetic nanoparticle hyperthermia

Using simulation to accurately design a heating protocol in magnetic nanoparticle hyperthermia relies on not only the initial nanoparticle distribution, but also the dynamic particle migration during heating. A coupled theoretical framework consisting of nanoparticle migration in a porous medium model and temperature elevation in a heat transfer model was developed to evaluate possible nanoparticle redistribution during local heating. Five generated tumor models from microcomputed tomography (microCT) with nanoparticle deposition were used to predict temperature elevations and assess local thermal damage when each tumor was subject to an alternating magnetic field. Local thermal damage further changed the interstitial structure in the tumor, resulting in enhancements in porosity and diffusion coefficient to promote nanoparticle diffusion to low concentration regions. The distribution volumes of nanoparticles in the highest concentration range reduced after heating, while those in the lower concentration ranges increased. After heating, the total nanoparticle distribution volume defined as the tumor volume occupied by nanoparticles was 21% bigger than that before the heating. The theoretical predictions of nanoparticle migration trend agree well with experimental results of microCT scan analyses. It is concluded that thermal damage induced enhancement in nanoparticle diffusion may be one of the mechanisms to explain nanoparticle migration during magnetic nanoparticle hyperthermia. Results from this study may suggest a feasibility of enhancing nanoparticle dispersion from injection sites using deliberate thermal damage.

Magnetic nanoparticles hyperthermia in a non-adiabatic and radiating process

We investigate the magnetic nanoparticles hyperthermia in a non-adiabatic and radiating process through the calorimetric method. Specifically, we propose a theoretical approach to magnetic hyperthermia from a thermodynamic point of view. To test the robustness of the approach, we perform hyperthermia experiments and analyse the thermal behavior of magnetite and magnesium ferrite magnetic nanoparticles dispersed in water submitted to an alternating magnetic field. From our findings, besides estimating the specific loss power value from a non-adiabatic and radiating process, thus enhancing the accuracy in the determination of this quantity, we provide physical meaning to a parameter found in literature that still remained not fully understood, the effective thermal conductance, and bring to light how it can be obtained from experiment. In addition, we show our approach brings a correction to the estimated experimental results for specific loss power and effective thermal conductance, thus demonstrating the importance of the heat loss rate due to the thermal radiation in magnetic hyperthermia.

Magnetic Nanoparticle Hyperthermia for Cancer Treatment: a Review On Nanoparticle Types and Thermal Analyses

Abstract Magnetic nanoparticle hyperthermia (MNH) is a localized cancer treatment which uses an alternating magnetic field to excite magnetic nanoparticles (MNPs) injected into a tumor, causing them to generate heat. Once the temperature of the tumor tissue reaches about 43°C, the cancerous cells die. Different types of MNPs have been studied, including iron oxides with various coatings, Cu-Ni alloys and complex manganese/zinc particles. This paper reviews different types of MNPs and assesses them by magnetization, SAR, and Curie Temperature. We reviewed the achievements and limitations of the works in this field. A major issue with MNH is maintaining effective hyperthermia while preserving healthy tissue. Numerical modeling can predict temperature distribution and safely simulate hyperthermia. The most used bioheat transfer equation is Pennes' equation which includes a term for blood perfusion, an important factor for temperature distribution. While some models safely neglect it, most include blood perfusion term. Some recent models have also included large blood vessels, others used their own heat transfer models. This article reviews the different models and classifies them based on how they address blood flow. A need for studies with realistic tumor shapes was identified. The irregular shape of most tumors could result in less uniform temperature distribution than in the commonly used circular or spherical models. This article aims to identify potential future work to create more realistic tumor models.

A comparative study on the effects of increase in injection sites on the magnetic nanoparticles hyperthermia

The thermal response of the tumor tissue to MNPs hyperthermia can vary based on the configuration of the MNPs hyperthermia setup and its various parameters. Injection strategy highly influences the mass transfer in this treatment, which is one of the more important parameters associated with the success of the MNPs hyperthermia in cancer treatment. The goal of this study was to compare the mechanical response of the tumor tissue to single and three site injections. A numerical model of lower limb cancer tumor, based on CT images, was constructed to investigate this. The results of this study showed that while increasing injection sites slightly enhances the mass and heat transfer fluxes, they are much more significantly affected by the injection rate. The three-point injection did improve the nanoparticles and heat distribution by creating a more homogeneous distribution, which both increased the damage to tissue and decreased the risk of tissue necrosis.

Mild magnetic nanoparticle hyperthermia promotes the disaggregation and microglia-mediated clearance of beta-amyloid plaques

The formation of beta-amyloid (Aβ) plaques is a classical hallmark of Alzheimer's disease (AD) that is associated with the promotion of neuroinflammation and subsequent neurotoxicity. Given the limited therapeutic options for targeting and clearing Aβ plaques in AD, there is an urgent need to develop effective approaches to reduce plaque accumulation. The objective of this study was to validate mild magnetic nanoparticle (MNP) hyperthermia technology as a strategy to clear Aβ deposits and determine the impact on microglia functionality. Our results demonstrated that the heating of MNPs localized to Aβ aggregates upon exposure to high frequency alternating magnetic field (AMF) was sufficient to disrupt Aβ plaques, resulting in its fragmentation. Importantly, this could facilitate the phagocytic clearance of Aβ as well as attenuate pro-inflammatory responses by human microglial cells. Our results support the feasibility of mild MNP/AMF hyperthermia as a new strategy for reducing beta-amyloid burdens in Alzheimer's disease.