Structural, Magnetic and Heating Efficiency of Ball Milled γ-Fe2O3/Gd2O3 Nanocomposite for Magnetic Hyperthermia

The preparation of γ-Fe2O3/Gd2O3 nanocomposite for possible use in magnetic hyperthermia application was done by ball milling technique. The nanocomposite was characterized by X-ray diffraction (XRD) and vibrating sample magnetometer (VSM). The heating efficiency and the effect of milling time (5 h and 30 h) on the structural and magnetic properties of the nanocomposite were reported. XRD analysis confirms the formation of the nanocomposite, while magnetization measurements show that the milled sample present hysteresis with low coercivity and remanence. The specific absorption rate (SAR) under an alternating magnetic field is investigated as a function of the milling time. A mean heating efficiency of 68 W/g and 28.7 W/g are obtained for 5 h and 30 h milling times respectively at 332 kHz and 170 Oe. The results showed that the obtained nanocomposite for 5 h milling time is a promising candidate for magnetic hyperthermia due to his properties which show an interesting magnetic behavior and high specific absorption rate.

Extraction method of nanoparticles concentration distribution from magnetic particle image and its application in thermal damage of magnetic hyperthermia

Magnetic particle imaging(MPI)technology can generate a real-time magnetic nanoparticle(MNP)distribution image for biological tissues,and its use can overcome the limitations imposed in magnetic hyperthermia treatments by the unpredictable MNP distribution after the intratumoral injection of nanofluid.However,the MNP concentration distribution is generally difficult to be extracted from MPI images.This study proposes an approach to extract the corresponding concentration value of each pixel from an MPI image by a least squares method(LSM),which is then translated as MNP concentration distribution by an interpolation function.The resulting MPI-based concentration distribution is used to evaluate the treatment effect and the results are compared with the ones of two baseline cases under the same dose:uniform distribution and MPI-based distribution considering diffusion.Additionally,the treatment effect for all these cases is affected by the blood perfusion rate,which is also investigated deeply in this study.The results demonstrate that the proposed method can be used to effectively reconstruct the concentration distribution from MPI images,and that the weighted LSM considering a quartic polynomial for interpolation provides the best results with respect to other cases considered.Furthermore,the results show that the uniformity of MNP distribution has a positive correlation with both therapeutic temperature distribution and thermal damage degree for the same dose and a critical power dissipation value in the MNPs.The MNPs uniformity inside biological tissue can be improved by the diffusion behavior after the nanofluid injection,which can ultimately reflect as an improvement of treatment effect.In addition,the blood perfusion rate considering local temperature can have a positive effect on the treatment compared to the case which considers a constant value during magnetic hyperthermia.

Magnetic Particle Imaging for Magnetic Hyperthermia Treatment: Visualization and Quantification of the Intratumoral Distribution and Temporal Change of Magnetic Nanoparticles in Vivo

Purpose: Magnetic hyperthermia treatment (MHT) is a strategy for cancer therapy using the tem-perature rise of magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF). Re-cently, a new imaging method called magnetic particle imaging (MPI) has been introduced. MPI allows imaging of the spatial distribution of MNPs. The purpose of this study was to investigate the feasibility of visualizing and quantifying the intratumoral distribution and temporal change of MNPs and predicting the therapeutic effect of MHT using MPI. Materials and Methods: Colon-26 cells (1 × 106 cells) were implanted into the backs of eight-week-old male BALB/c mice. When the tumor volume reached approximately 100 mm3, mice were divided into untreated (n = 10) and treated groups (n = 27). The tumors in the treated group were directly injected with MNPs (Resovist?) with iron concentrations of 500 mM (A, n = 9), 400 mM (B, n = 8), and 250 mM (C, n = 10), respectively, and MHT was performed using an AMF with a frequency of 600 kHz and a peak amplitude of 3.5 kA/m. The mice in the treated group were scanned using our MPI scanner immediately before, immediately after, 7 days, and 14 days after MHT. We drew a region of interest (ROI) on the tumor in the MPI image and calculated the average, maximum, and total MPI values and the number of pixels by taking the threshold value for extracting the contour as 40% of the maximum MPI value (pixel value) within the ROI. These parameters in the untreated group were taken as zero. We also measured the relative tumor volume growth (RTVG) defined by (V-V0)/V0, where V0 and V are the tumor volumes immediately before and after MHT, respectively. Results: The average, maximum, and total MPI values decreased up to 7 days after MHT and remained almost constant thereafter in all groups, whereas the number of pixels tended to increase with time. The RTVG values in Groups A and B were significantly lower than those in the control group 3 days or more and 5 days or more after MHT, respectively. The above four parameters were significantly inversely correlated with the RTVG values 5, 7, and 14 days after MHT. Conclusion: MPI can visualize and quantify the intratumoral distribution and temporal change of MNPs before and after MHT. Our results suggest that MPI will be useful for predicting the therapeutic effect of MHT and for the treatment planning of MHT.

Thermal apoptosis analysis considering injection behavior optimization and mass diffusion during magnetic hyperthermia

Thermally induced apoptosis for tumors depends mainly on the intrinsic characteristics of biological tissues as well as treatment temperature profile during magnetic hyperthermia.Further,treatment temperature distribution inside tumor depends on the injection behavior of irregular tumors,such as the injection dose and the injection location of nanofluids.In order to improve the treatment effect,the simulated annealing algorithm is adopted in this work to optimize the nanofluid injection behavior,and the improved Arrhenius model is used to evaluate the malignant ablations for three typical malignant tumor cell models.In addition,both the injection behavior optimization and the mass diffusion of nanofluid are both taken into consideration in order to improve the treatment effect.The simulation results demonstrate that the injection behavior can be optimized effectively by the proposed optimization method before therapy,the result of which can also conduce to improving the thermal apoptosis possibility for proposed typical malignant cells.Furthermore,an effective approach is also employed by considering longer diffusion duration and correct power dissipation at the same time.The results show that a better result can then be obtained than those in other cases when the power dissipation of MNPs is set to be QMNP=5.4×10^(7)W·m^(3) and the diffusion time is 16 h.

Effects of dipolar interactions on the magnetic hyperthermia of Zn_(0.3)Fe_(2.7)O_(4) nanoparticles with different sizes

Tumor-targeted magnetic hyperthermia has recently attracted much attention.Magnetic nanoparticles(NPs) are heat mediator nanoprobes in magnetic hyperthermia for cancer treatment.In this paper,single cubic spinel structural Zn_(0.3)Fe_(2.7)O_(4) magnetic NPs with sizes of 14 nm-20 nm were synthesized,followed by coating with SiO_(2) shell.The SLP value of Zn_(0.3)Fe_(2.7)O_(4)/SiO_(2) NPs below 20 nm changes non-monotonically with the concentration of solution under the alternating current(AC) magnetic field of 430 kHz and 27 kA/m.SLP values of all Zn_(0.3)Fe_(2.7)O_(4)/SiO_(2) NPs appear a peak value with change of solution concentration.The solution concentrations with optimal SLP value decrease with increasing magnetic core size.This work can give guidance to the better prediction and control of the magnetic hyperthermia performance of materials in clinical applications.

Hierarchical lichee-like Fe_(3)O_(4) assemblies and their high heating efficiency in magnetic hyperthermia

A nontoxic and biocompatible thermoseed is developed for the magnetic hyperthermia.Two kinds of thermoseed materials:hierarchical hollow and solid lichee-like Fe_(3)O_(4) assemblies,are synthesized by a facile hydrothermal method.The crystal structure of Fe_(3)O_(4) assemblies are characterized by x-ray diffraction,scanning electron microscopy,and transmission electron microscopy.Moreover,the prepared Fe_(3)O_(4) assemblies are used as a magnetic heat treatment agent,and their heating efficiency is investigated.Compared to solid assembly,hollow lichee-like Fe_(3)O_(4) assembly exhibits a higher specific absorption rate of 116.53 W/g and a shorter heating time,which is ascribed to its higher saturation magnetization,larger initial particle size,and the unique hierarchical hollow structure.Furthermore,the magnetothermal effect is primarily attributed to Neel relaxation.Overall,we propose a facile and convenient approach to enhance the heating efficiency of magnetic nanoparticles by forming hollow hierarchical assemblies.

A Simulation Study on the Specific Loss Power in Magnetic Hyperthermia in the Presence of a Static Magnetic Field

Our purpose in this study was to present a method for estimating the specific loss power (SLP) in magnetic hyperthermia in the presence of an external static magnetic field (SMF) and to investigate the SLP values estimated by this method under various diameters (D) of magnetic nanoparticles (MNPs) and amplitudes (H0) and frequencies (f) of an alternating magnetic field (AMF). In our method, the SLP was calculated by solving the magnetization relaxation equation of Shliomis numerically, in which the magnetic field strength at time t (H(t)) was assumed to be given by , with Hs being the strength of the SMF. We also investigated the SLP values in the case when the SMF with a field-free point (FFP) generated by two solenoid coils was used. The SLP value in the quasi steady state (SLPqss) decreased with increasing Hs. The plot of the SLPqss values against the position from the FFP became narrow as the gradient strength of the SMF (Gs) increased. Conversely, it became broad as Gs decreased. These results suggest that the temperature rise and the area of local heating in magnetic hyperthermia can be controlled by varying the Hs and Gs values, respectively. In conclusion, our method will be useful for estimating the SLP in the presence of both the AMF and SMF and for designing an effective local heating system for magnetic hyperthermia in order to reduce the risk of overheating surrounding healthy tissues.

Methods for Estimating Specific Loss Power in Magnetic Hyperthermia Revisited

Our purpose in this study was to present three methods for estimating specific loss power (SLP) in magnetic hyperthermia with use of an alternating magnetic field (AMF) and magnetic nanoparticles (MNPs) and to compare the SLP values estimated by the three methods using simulation studies under various diameters of MNPs (D), amplitudes (H0) and frequencies of AMF (f). In the first method, the SLP was calculated by solving the magnetization relaxation equation of Shliomis numerically (SLP1). In the second method, the SLP was obtained by solving Shliomis’ relaxation equation using the complex susceptibility (SLP2). The third method was based on Rosensweig’s model (SLP3). The SLP3 value changed largely depending on the magnetic field strength (H) in the Langevin parameter (§) and it became maximum (SLP3max) and minimum (SLP3min) when H was 0 and ±H0, respectively. The relative difference between SLP1 and SLP2 was the largest and increased with increasing D and H0, whereas that between SLP1 and was the smallest and was almost constant regardless of D and H0, suggesting that H in ξ should be taken as H0 in estimating the SLP using Rosensweig’s model. In conclusion, this study will be useful for optimizing the parameters of AMF in magnetic hyperthermia and for the optimal design of MNPs for magnetic hyperthermia.

A single magnetic nanoplatform-mediated combination therapy of immune checkpoint silencing and magnetic hyperthermia for enhanced anti-cancer immunity

As a revolutionary cancer treatment strategy,immunotherapy has attracted great attention.However,the effect of immunotherapy such as immune checkpoint blockade(ICB)is usually limited by insufficient immune response in the body.Herein,a polycation-based magnetic nanocluster platform was developed to load therapeutic nucleic acids,which could achieve gene therapy-mediated ICB and efficient magnetic hyperthermia therapy(MHT).The silencing of immune checkpoints together with MHT-induced immunogenic cell death(ICD)effectively alleviated the immune escape of cancer cells and significantly enhanced the visibility of cancer cells to the immune system.This combined treatment strategy activated a strong adaptive anti-cancer immune response in vivo,greatly inhibiting tumor growth,metastasis and recurrence.

M2 macrophage-targeted iron oxide nanoparticles for magnetic resonance image-guided magnetic hyperthermia therapy

Tumor-associated macrophages(TAMs)play an important role in tumor development and progression.In particular,M2 TAMs can promote tumor growth by facilitating tumor progression and malignant behaviors.Selectively targeted elimination of M2 TAMs to inhibit tumor progression is of great significance for cancer treatment.Iron oxide nanoparticles based magnetic hyperthermia therapy(MHT)is a classical approach to destroy tumor tissue with deep penetration depth.In this study,we developed a typical M2 macrophage-targeted peptide(M2pep)functionalized superparamagnetic iron oxide nanoparticle(SPIO)for magnetic resonance imaging(MRI)-guided MHT in an orthotopic breast cancer mouse model.The obtained multifunctional SPIO-M2pep with a hydrodynamic diameter of 20 nm showed efficient targeting capability,high transverse relaxivity(149 mM^(-1) s^(-1))and satisfactory magnetic hyperthermia performance in vitro.In vivo studies demonstrated that the SPIO-M2pep based MRI can monitor the distribution of nanoparticles in tumor and indicate the suitable timing for MHT.The M2 macrophage-targeted MHT significantly reduced the tumor volume and the population of pro-tumoral M2 TAMs in tumor.In addition,the SPIO-M2pep based MHT can remodel the tumor immune microenvironment(TIME).The multifunctional SPIO-M2pep with M2 macrophage-targeting ability,high magnetic hyperthermia efficiency,MR imaging capability and effective role in remodeling the TIME hold great potential to improve clinical cancer therapy outcomes.

Enhanced hyperthermia performance in hard-soft magnetic mixed Zn0.5CoxFe2.5−xO4/SiO2 composite magnetic nanoparticles

High quality Zn0.5CoxFe2.5−xO4(x=0,0.05,0.1,0.15)serial magnetic nanoparticles with single cubic structures were prepared by the modified thermal decomposition method,and Zn0.5CoxFe2.5−xO4/SiO2 composite magnetic nanoparticles were prepared by surface modification of SiO2.The magnetic anisotropy of the sample increases with the increase of the doping amount of Co2+.When the doping amount is 0.1,the sample shows the transition from superparamagnetism to ferrimagnetism at room temperature.In the Zn0.5CoxFe2.5−xO4/SiO2 serial samples,the maximum value of specific loss power(SLP)with 1974 W/gmetal can also be found at doping amount of x=0.1.The composite nanoparticles are expected to be an excellent candidate for clinical magnetic hyperthermia.

Magnetite Nanoparticles Coated with Synthetic Polymer for Hyperthermia Application: Review

Hyperthermia treatment using appropriate magnetic materials in an alternating magnetic field to generate heat has been proposed as a low-invasive cancer treatment method. Magnetite iron oxide nanoparticles (Fe3O4) are expected to be an appropriate type of magnetic material for this purpose due to its biocompatibility. Several polymers are used to Fe3O4 MNPs to avoid or decrease agglomeration, and in most cases increase dispersion stability. In this review, we will give briefly how these coated magnetite nanoparticles (PMNPs) are synthesized in the first part. The main characterization techniques usually used to study the properties of these MNPs are prseneted in the second part. Finally, most recent results on the heating ability of polymeric coated magnetite nanoparticles (PMNPs) are given in the last part of this review.

Novel magnetic vortex nanorings/nanodiscs: Synthesis and theranostic applications

Recent discoveries in the synthesis and applications of magnetic vortex nanorings/nanodiscs in theranostic applications are reviewed. First, the principles of nanomagnetism and magnetic vortex are introduced. Second, methods for producing magnetic vortex nanorings/nanodiscs are presented. Finally, theranostic applications of magnetic vortex nanorings/nanodiscs are addressed.

Magnetic nanoparticle-based cancer therapy

Nanoparticles（NPs） with easily modified surfaces have been playing an important role in biomedicine.As cancer is one of the major causes of death,tremendous efforts have been devoted to advance the methods of cancer diagnosis and therapy.Recently,magnetic nanoparticles（MNPs） that are responsive to a magnetic field have shown great promise in cancer therapy.Compared with traditional cancer therapy,magnetic field triggered therapeutic approaches can treat cancer in an unconventional but more effective and safer way.In this review,we will discuss the recent progress in cancer therapies based on MNPs,mainly including magnetic hyperthermia,magnetic specific targeting,magnetically controlled drug delivery,magnetofection,and magnetic switches for controlling cell fate.Some recently developed strategies such as magnetic resonance imaging（MRI） monitoring cancer therapy and magnetic tissue engineering are also addressed.

Evaluating physical changes of iron oxide nanoparticles due to surface modification with oleic acid

The physical characterization of a colloidal system of superficially modified magnetic nanoparticles (MNPs) is presented. The system consists of oleic acid-coated iron oxide nanoparticles (OAMNP) suspended in water. A structural analysis is carried out by using standard physical techniques to determine the diameter and shape of the MNPs and also the width of the coating shell. The colloidal stability and the polydispersity index of this ferrofluid are determined by using Zeta potential measurements. Additionally, the magnetic characterization is conducted by obtaining the DC magnetization loops, and the blocking temperatures are determined according to the ZFC–FC protocol. Finally, the values of power absorption density P of the ferrofluid are estimated by using a magneto-calorimetric procedure in a wide range of magnetic field amplitude H and frequency f. The experimental results exhibit spherical-like shape of OAMNP with (20 ± 4) nm in diameter. Due to the use of coating process, the parameters of the magnetization loops and the blocking temperatures are significantly modified. Hence, while the uncoated MNPs show a blocking state of the magnetization, the OAMNP are superparamagnetic above room temperature (300 K). Furthermore, the reached dependence P versus f and P versus H of the ferrofluid with coated MNPs are clearly fitted to linear and quadratic correlations, respectively, showing their accordance with the linear response theory.

Nanomagnetism:Principles,nanostructures,and biomedical applications

Nanomagnetism is the origin of many unique properties in magnetic nanomaterials that can be used as building blocks in information technology, spintronics, and biomedicine. Progresses in nanomagnetic principles, distinct magnetic nanostructures, and the biomedical applications of nanomagnetism are summarized.

Magnetic systems for cancer immunotherapy

Immunotherapy is a rapidly developing area of cancer treatment due to its higher specificity and potential for greater efficacy than traditional therapies.Immune cell modulation through the administration of drugs,proteins,and cells can enhance antitumoral responses through pathways that may be otherwise inhibited in the presence of immunosuppressive tumors.Magnetic systems offer several advantages for improving the performance of immunotherapies,including increased spatiotemporal control over transport,release,and dosing of immunomodulatory drugs within the body,resulting in reduced off-target effects and improved efficacy.Compared to alternative methods for stimulating drug release such as light and pH,magnetic systems enable several distinct methods for programming immune responses.First,we discuss how magnetic hyperthermia can stimulate immune cells and trigger thermoresponsive drug release.Second,we summarize how magnetically targeted delivery of drug carriers can increase the accumulation of drugs in target sites.Third,we review how biomaterials can undergo magnetically driven structural changes to enable remote release of encapsulated drugs.Fourth,we describe the use of magnetic particles for targeted interactions with cellular receptors for promoting antitumor activity.Finally,we discuss translational considerations of these systems,such as toxicity,clinical compatibility,and future opportunities for improving cancer treatment.

Magnetic lipid nanovehicles synergize the controlled thermal release of chemotherapeutics with magnetic ablation while enabling non-invasive monitoring by MRI for melanoma theranostics

Nowadays,a number of promising strategies are being developed that aim at combining diagnostic and therapeutic capabilities into clinically effective formulations.Thus,the combination of a modified release provided by an organic encapsulation and the intrinsic physico-chemical properties from an inorganic counterpart opens new perspectives in biomedical applications.Herein,a biocompatible magnetic lipid nanocomposite vehicle was developed through an efficient,green and simple method to simultaneously incorporate magnetic nanoparticles and an anticancer drug(doxorubicin)into a natural nano-matrix.The theranostic performance of the final magnetic formulation was validated in vitro and in vivo,in melanoma tumors.The systemic administration of the proposed magnetic hybrid nanocomposite carrier enhanced anti-tumoral activity through a synergistic combination of magnetic hyperthermia effects and antimitotic therapy,together with MRI reporting capability.The application of an alternating magnetic field was found to play a dual role,(i)acting as an extra layer of control(remote,on-demand)over the chemotherapy release and(ii)inducing a local thermal ablation of tumor cells.This combination of chemotherapy with thermotherapy establishes a synergistic platform for the treatment of solid malignant tumors under lower drug dosing schemes,which may realize the dual goal of reduced systemic toxicity and enhanced anti-tumoral efficacy.

Controlled temperature-mediated curcumin release from magneto-thermal nanocarriers to kill bone tumors

Systemic chemotherapy has lost its position to treat cancer over the past years mainly due to drug resistance,side effects,and limited survival ratio.Among a plethora of local drug delivery systems to solve this issue,the combinatorial strategy of chemo-hyperthermia has recently received attention.Herein we developed a magneto-thermal nanocarrier consisted of superparamagnetic iron oxide nanoparticles(SPIONs)coated by a blend formulation of a three-block copolymer Pluronic F127 and F68 on the oleic acid(OA)in which Curcumin as a natural and chemical anti-cancer agent was loaded.The subsequent nanocarrier SPION@OA-F127/F68-Cur was designed with a controlled gelation temperature of the shell,which could consequently control the release of curcumin.The release was systematically studied as a function of temperature and pH,via response surface methodology(RSM).The bone tumor killing efficacy of the released curcumin from the carrier in combination with the hyperthermia was studied on MG-63 osteosarcoma cells through Alamar blue assay,live-dead staining and apoptosis caspase 3/7 activation kit.It was found that the shrinkage of the F127/F68 layer stimulated by elevated temperature in an alternative magnetic field caused the curcumin release.Although the maximum release concentration and cell death took place at 45℃,treatment at 41℃ was chosen as the optimum condition due to considerable cell apoptosis and lower side effects of mild hyperthermia.The cell metabolic activity results confirmed the synergistic effects of curcumin and hyperthermia in killing MG-63 osteosarcoma cells.