Magnetic Multicore Nanoparticles Research Articles

Insight into the Internal Structure of High-Performance Multicore Magnetic Nanoparticles Used in Cancer Thermotherapy.

Multicore magnetic nanoparticles (MNPs), comprising iron oxide cores embedded in a sugar or starch matrix, are a class of nanomaterials with promising magnetic heating properties. Their internal structure, and particularly the strength of the internal core-core magnetic interactions, are believed to determine the functional properties, but there have been few detailed studies on this to date. We report here on an interlaboratory and multimodality transmission electron microscopy (TEM) and magnetic study of a high-performance MNP material (supplied by Resonant Circuits Limited, RCL) that is currently being used in a clinical study for the treatment of pancreatic cancer. TEM data were collected under a variety of conditions: conventional; high-resolution; scanning; cryogenic; and, for the first time, liquid phase. All the imaging modes showed mostly irregular dextran lamellae of lateral dimensions 30-90 nm, plus ca. 15% n/n of what appeared to be 30-60 nm long "nanorods", and a multitude of well-dispersed ca. 3.7 nm diameter iron oxide cores. Cryogenic electron tomography indicated that the nanorods were edge-on lamellae, but in dried samples, tomography showed rod- or lath-shaped forms, possibly resulting from the collapse of lamellae during drying. High-resolution TEM (HRTEM) showed the dextran to be crystallized in the low-temperature hydrated dextran polymorph. Magnetic remanence Henkel-plot analysis indicated a weak core-core interaction field of ca. 4.8 kA/m. Theoretical estimates using a point-dipole model associated this field with a core-to-core separation distance of ca. 5 nm, which tallies well with the ca. 4-6 nm range of separation distances observed in liquid-cell TEM data. On this basis, we identify the structure-function link in the RCL nanoparticles to be the unusually well-dispersed multicore structure that leads to their strong heating capability. This insight provides an important design characteristic for the future development of bespoke nanomaterials for this significant clinical application.

Microwave susceptibility analysis of ultrafast moment dynamics in a multicore magnetic nanoparticle system

Room-temperature magnetization dynamics of multicore magnetic nanoparticles often account for intrinsic dipolar magnetism to behave as a single macrospin at low-frequency regime. Either magnetic particle imaging or hyperthermia benefits from the resulting superparamagnetism in terms of nonlinear magnetization response and relaxation losses at frequencies where the rotation of magnetic moments dominates over Brownian motion for a given sinusoidal field. For this situation, spontaneous thermal relaxation (in the absence of external fields) of each composing particle moment within the cluster is critical to define effective Néel time constant and may intersect with ferromagnetic resonance (FMR) at GHz range. Here, we performed broadband AC susceptometry on both immobilized single-core and multicore iron-oxide nanoparticles up to 26.5GHz under DC bias fields. For each solid sample, we confirmed FMR frequency, where large single-core nanoparticle systems demonstrated typical resonance blueshift as DC field increased. Interestingly, high DC field induced the secondary satellite peak in the imaginary part of AC susceptibility spectra for the case of multicore nanoparticle systems. We further highlighted that a synchronous precession of the polarized macrospins under nonuniform effective fields was responsible for splitting FMR peaks at nearby microwave frequencies. Upon curve fitting of the field-dependent FMR frequency spectra, the Landau-Lifshitz-Gilbert-Kittel model later elaborates on the complex moment dynamics of multicore nanoparticle systems in correlation with distribution functions. Published by the American Physical Society 2024

Cellular and Molecular Processes Are Differently Influenced in Primary Neural Cells by Slight Changes in the Physicochemical Properties of Multicore Magnetic Nanoparticles

Herein, we use two exemplary superparamagnetic iron oxide multicore nanoparticles (SPIONs) to illustrate the significant influence of slightly different physicochemical properties on the cellular and molecular processes that define SPION interplay with primary neural cells. Particularly, we have designed two different SPION structures, NFA (i.e., a denser multicore structure accompanied by a slightly less negative surface charge and a higher magnetic response) and NFD (i.e., a larger surface area and more negatively charged), and identified specific biological responses dependent on SPION type, concentration, exposure time, and magnetic actuation. Interestingly, NFA SPIONs display a higher cell uptake, likely driven by their less negative surface and smaller protein corona, more significantly impacting cell viability and complexity. The tight contact of both SPIONs with neural cell membranes results in the significant augmentation of phosphatidylcholine, phosphatidylserine, and sphingomyelin and the reduction of free fatty acids and triacylglycerides for both SPIONs. Nonetheless, NFD induces greater effects on lipids, especially under magnetic actuation, likely indicating a preferential membranal location and/or a tighter interaction with membrane lipids than NFA, in agreement with their lower cell uptake. From a functional perspective, these lipid changes correlate with an increase in plasma membrane fluidity, again larger for more negatively charged nanoparticles (NFD). Finally, the mRNA expression of iron-related genes such as Ireb-2 and Fth-1 remains unaltered, while TfR-1 is only detected in SPION-treated cells. Taken together, these results demonstrate the substantial impact that minor physicochemical differences of nanomaterials may exert in the specific targeting of cellular and molecular processes. A denser multicore structure generated by autoclave-based production is accompanied by a slight difference in surface charge and magnetic properties that become decisive for the biological impact of these SPIONs. Their capacity to markedly modify the lipidic cell content makes them attractive as lipid-targetable nanomedicines.

Optimization of cobalt ferrite magnetic nanoparticle as a theranostic agent: MRI and hyperthermia.

Magnetic nanoparticles (MNPs) are considered a theranostic agent in MR imaging, playing an effective role in inducing magnetic hyperthermia. Since, high-performance magnetic theranostic agents are characterized by superparamagnetic behavior and high anisotropy, in this study, cobalt ferrite MNPs were optimized and investigated as a theranostic agent. CoFe2O4@Au@dextran particles were synthesized and characterized by DLS, HRTEM, SEM, XRD, FTIR, and VSM methods. After cytotoxicity evaluation, MR imaging parameters (r1, r2 and r2 / r1) were calculated for these nanostructures. Afterward, magnetic hyperthermia at the frequency of 425kHz was applied to calculate specific loss power (SLP). Formation of CoFe2O4@Au@dextran was confirmed by UV-Visible spectrophotometry. On the basis of the relaxometric and hyperthermia induction findings of nanostructures in all stages of synthesis, the CoFe2O4@Au@dextran could produce the highest parameters of r2 and r2/r1 and SLP with values ​​of 389.7, 51.2mM-1s-1, and 2449 W/g, respectively. The formation of multi-core MNPs by dextran coating is expected to improve the magnetic properties of the nanostructure, leading to optimization of theranostic parameters, so that CoFe2O4@Au@dextran NPs can create contrast-enhanced images more than three times the clinical use and require less contrast agent, reducing side effects. Accordingly, CoFe2O4@Au@dextrancan be introduced as a suitable theranostic nanostructurewith optimal efficiency.

Multicore-based ferrofluids in zero field: initial magnetic susceptibility and self-assembly mechanisms.

The necessity to improve magnetic building blocks in magnetic nano-structured soft materials stems from a fascinating potential these materials have in bio-medical applications and nanofluidics. Along with practical reasons, the interplay of magnetic and steric interactions on one hand, and entropy, on the other, makes magnetic soft matter fundamentally challenging. Recently, in order to tailor magnetic response of the magnetic particle suspensions, the idea arose to replace standard single-core nanoparticles with nano-sized clusters of single-domain nanoparticles (grains) rigidly bound together by solid polymer matrix - multicore magnetic nanoparticles (MMNPs). To pursue this idea, a profound understanding of the MMNP interactions and self-assembly is required. In this work we present a computational study of the MMNP suspensions and elucidate their self-assembly and magnetic susceptibility. We show that depending on the magnetic moment of individual grains the suspensions exhibit qualitatively distinct regimes. Firstly, if the grains are moderately interacting, they contribute to a significant decrease of the remanent magnetisation of MMNPs and as such to a decrease of the magnetic susceptibility, this way confirming previous findings. If the grains are strongly interacting, instead, they serve as anchor points and support formation of grain clusters that span through several MMNPs, leading to MMNP cluster formation and a drastic increase of the initial magnetic response. Both the topology of the clusters and their size distribution in MMNP suspensions is found to be notably different from those formed in conventional magnetic fluids or magnetorheological suspensions.

Frequency and Amplitude Optimizations for Magnetic Particle Spectroscopy Applications

Nowadays, there is a growing interest in the field of magnetic particle spectroscopy (MPS)-based bioassays. MPS monitors the dynamic magnetic response of surface-functionalized magnetic nanoparticles (MNPs) upon excitation by an alternating magnetic field (AMF) to detect various target analytes. This technology has flourished in the past decade due to its low cost, low background magnetic noise interference from the biomatrix, and fast response time. A large number of MPS variants have been reported by different groups around the world, with applications ranging from disease diagnosis to foodborne pathogen detection and virus detection. However, there is an urgent need for guidance on how to optimize the sensitivity of MPS detection by choosing different types of MNPs, AMF modalities, and MPS assay strategies (i.e., volume- and surface-based assays). In this work, we systematically study the effect of AMF frequencies and amplitudes on the responses of single- and multicore MNPs under two extreme conditions, namely, the bound and unbound states. Our results show that some modalities such as dual-frequency MPS utilizing multicore MNPs are more suitable for surface-based bioassay applications, whereas single-frequency MPS systems using single- or multicore MNPs are better suited for volumetric bioassay applications. Furthermore, the bioassay sensitivities for these modalities can be further improved by a careful selection of AMF frequencies and amplitudes.

Plasmonic/magnetic liposomes based on nanoparticles with multicore-shell architecture for chemo/thermotherapy

Multifunctional nanosystems are capable to carry one or more therapeutic agents (thermal and/or targeting agents and chemotherapeutic drugs), offering the capability to concurrently perform different treatment modalities using a single nanosystem. Cluster nanostructures, consisting of densely packed aggregates of magnetic nanoparticles, have shown enhanced heating capabilities. Their combination with plasmonic nanoparticles enable synergistic behavior between dual hyperthermia (magneto-photothermia), allowing overheating cancer cells while increasing drug toxicity. In this work, multicore magnetic nanoparticles (NPs) of MnFe2O4 were prepared using oxamide and melamine as clustering agents. The multicore NPs prepared with oxamide were covered with a gold shell, resulting in multicore magnetic/plasmonic NPs with an increased SAR of 173.80 W/g, under NIR light. Liposomes based on these magnetic/plasmonic NPs were prepared and the model drug curcumin was loaded in these nanocarriers with a high encapsulation efficiency. The fusion between the curcumin-loaded magnetic/plasmonic liposomes and models of cell membranes (labelled with Nile Red) was confirmed by FRET, pointing the magneto/plasmonic liposomes as promising for dual cancer therapy (combined hyperthermia and chemotherapy).

Structural and magnetic equilibrium properties of a semi-dilute suspension of magnetic multicore nanoparticles

The idea to create smart magnetically controllable nanostructured materials is highly appealing from both fundamental science point of view and application perspectives. Ample investigations of single-domain magnetic nanoparticles embedded in liquid and gel-like magneto-passive carriers revealed a plethora of new phenomena from controllable equilibrium self-assembly to a designed heat dissipation on the application of AC magnetic fields. However, all the effects in such systems are limited by the physical energy and entropy scales of nanoparticles and are very sensitive to temperature changes and confinement. As a result, among new types of complex magnetic materials, magnetic multicore nanoparticles (MMNPs) made of rigidly bound single-domain nanograins were proposed. The properties of such systems are resulting from inter-grain and grain-field interactions, and are not yet fully understood. In this study, employing Langevin dynamics computer simulations, we analyse the interplay of the aforementioned interactions in a dilute suspension of MMNPs made of grains with negligible magnetic anisotropy. We find that the stronger are the inter-grain interactions the lower is the initial magnetic response of MMNPs. The response is though hindered, rather than suppressed: at a certain intensity of an applied magnetic field a sufficient degree of the alignment of the grain magnetic moments and the field is achieved and a large-scale self-assembly accompanied by a rapid growth of magnetisation is observed. The strength of interactions essential for this crossover is much higher than that for a suspension of single-domain grains with the same concentration and magnetic saturation.

Magnetoliposomes Containing Multicore Nanoparticles and a New Antitumor Thienopyridine Compound with Potential Application in Chemo/Thermotherapy.

Multicore magnetic nanoparticles of manganese ferrite were prepared using carboxymethyl dextran as an agglutinating compound or by an innovative method using melamine as a cross-coupling agent. The nanoparticles prepared using melamine exhibited a flower-shape structure, a saturation magnetization of 6.16 emu/g and good capabilities for magnetic hyperthermia, with a specific absorption rate (SAR) of 0.14 W/g. Magnetoliposome-like structures containing the multicore nanoparticles were prepared, and their bilayer structure was confirmed by FRET (Förster Resonance Energy Transfer) assays. The nanosystems exhibited sizes in the range of 250–400 nm and a low polydispersity index. A new antitumor thienopyridine derivative, 7-[4-(pyridin-2-yl)-1H-1,2,3-triazol-1-yl]thieno[3,2-b]pyridine, active against HeLa (cervical carcinoma), MCF-7 (breast adenocarcinoma), NCI-H460 (non-small-cell lung carcinoma) and HepG2 (hepatocellular carcinoma) cell lines, was loaded in these nanocarriers, obtaining a high encapsulation efficiency of 98 ± 2.6%. The results indicate that the new magnetoliposomes can be suitable for dual cancer therapy (combined magnetic hyperthermia and chemotherapy).

Tailored Magnetic Multicore Nanoparticles for Use as Blood Pool MPI Tracers

For the preclinical development of magnetic particle imaging (MPI) in general, and the exploration of possible new clinical applications of MPI in particular, tailored MPI tracers with surface properties optimized for the intended use are needed. Here we present the synthesis of magnetic multicore particles (MCPs) modified with polyethylene glycol (PEG) for use as blood pool MPI tracers. To achieve the stealth effect the carboxylic groups of the parent MCP were activated and coupled with pegylated amines (mPEG-amines) with different PEG-chain lengths from 2 to 20 kDa. The resulting MCP-PEG variants with PEG-chain lengths of 10 kDa (MCP-PEG10K after one pegylation step and MCP-PEG10K2 after a second pegylation step) formed stable dispersions and showed strong evidence of a successful reaction of MCP and MCP-PEG10K with mPEG-amine with 10 kDa, while maintaining their magnetic properties. In rats, the mean blood half-lives, surprisingly, were 2 and 62 min, respectively, and therefore, for MCP-PEG10K2, dramatically extended compared to the parent MCP, presumably due to the higher PEG density on the particle surface, which may lead to a lower phagocytosis rate. Because of their significantly extended blood half-life, MCP-PEG10K2 are very promising as blood pool tracers for future in vivo cardiovascular MPI.

Curcuminoids-conjugated multicore magnetic nanoparticles: Design and characterization of a potential theranostic nanoplatform

Theranostic systems have gained much attention due to their widespread biological and technological applications. In this work, we report the synthesis and characterization of a theranostic nanoplatform based on multicore magnetic iron oxide functionalized with curcuminoids (CC) and coated with silica (MNP-CC@SiO2). The physicochemical and colloidal properties of the unloaded-curcuminoids nanoplatform (MNP@SiO2) were evaluated by several techniques, including X-ray diffraction, magnetometry measurements, transmission electron microscopy, and zeta potential and dynamic light scattering. The time and maximum loading of curcuminoids onto multicore MNP (MNP-CC) were investigated by adsorption kinetic and isotherm. After the curcuminoids loading, MNP-CC was coated with amorphous silica to prevent pervasion, degradation of the curcuminoids, and providing colloidal stabilization to the system. The resulting MNP-CC@SiO2 exhibits expressive fluorescence, in addition to interesting magnetic and thermal properties. On the other hand, this device shows a negligible release of curcuminoids in sink conditions. The potential theranostic features of MNP-CC@SiO2 nanoplatform are attributed to the combination of a multicore magnetic structure with a silica coating. We argue that this should provide a versatile and multifunctional nanoplatform. It is expected to present potential biomedical applications, such as image contrast, magnetic hyperthermia treatment, cell separation, and drug delivery.

Properties of single- and multi-core magnetic nanoparticles assessed by magnetic susceptibility measurements

Characterization of structural and magnetic properties of MNP ensembles is crucial in tailoring their performance for biomedical applications. In this work, we evaluate the size distribution of magnetic cores in single- and multi-core nanoparticles in water suspension using transmission electron microscopy (TEM) and static magnetization curve, with the geometrical core size ranges from 8.3 to 40.2 nm. A reasonable core size derived from the magnetization curve is obtained in comparison to the geometrical size from TEM image. The magnetic moment distribution possibly reveals that the reduction of effective magnetic core size is due to the magnetization degradation in cores. The hydrodynamic size and average anisotropy energy ratio obtained from the AC susceptibility response of MNPs from 5 Hz to 100 kHz are also evaluated. The complex distribution of relaxation time is constructed by applying a non-negative least square method to an AC susceptibility model that incorporates the inter- and intra-potential-well contributions. It is found that a log-normal distribution might not be adequate to represent the hydrodynamic size distribution reconstructed from the AC susceptibility responses of the suspended samples. It is demonstrated that the AC susceptibility model used in this study can be used to fairly estimate the average anisotropy energy ratio for MNP ensembles dominated by thermally blocked particles. Moreover, it can be suggested that besides the geometrical core size, the degree of core aggregation also plays an important role in determining the anisotropy energy ratio and effective magnetic moment.

Investigation of magnetically driven passage of magnetic nanoparticles through eye tissues for magnetic drug targeting

This paper elucidates the feasibility of magnetic drug targeting to the eye by using magnetic nanoparticles (MNPs) to which pharmaceutical drugs can be linked. Numerical simulations revealed that a magnetic field gradient of 20 T m−1 seems to be promising for dragging magnetic multicore nanoparticles of about 50 nm into the eye. Thus, a targeting magnet system made of superconducting magnets with a magnetic field gradient at the eye of about 20 T m−1 was simulated. For the proof-of-concept tissue experiments presented here the required magnetic field gradient of 20 T m−1 was realized by a permanent magnet array. MNPs with an optimized multicore structure were selected for this application by evaluating their stability against agglomeration of MNPs with different coatings in water for injections, physiological sodium chloride solution and biological media such as artificial tear fluid. From these investigations, starch turned out to be the most promising coating material because of its stability in saline fluids due to its steric stabilization mechanism. To evaluate the passage of MNPs through the sclera and cornea of the eye tissues of domestic pigs (Sus scrofa domesticus), a three-dimensionally printed setup consisting of two chambers (reservoir and target chamber) separated by the eye tissue was developed. With the permanent magnet array emulating the magnetic field gradient of the superconducting setup, experiments on magnetically driven transport of the MNPs from the reservoir chamber into the target chamber via the tissue were performed. The resulting concentration of MNPs in the target chamber was determined by means of quantitative magnetic particle spectroscopy. It was found that none of the tested particles passed the cornea, but starch-coated particles could pass the sclera at a rate of about 5 ng mm−2 within 24 h. These results open the door for future magnetic drug targeting to the eye.

Static magnetic response of multicore particles.

We present theoretical calculations of the characteristics of the static magnetic response of multicore magnetic nanoparticles. These particles contain a considerable number (∼10^{2}) of single-domain magnetic nanocrystallites, which are modeled as uniformly magnetized balls with uniaxial magnetocrystalline anisotropy, the energetic barrier of which is comparable with the thermal energy. Thus, we model a multicore magnetic nanoparticle as an ensemble of superparamagnetic nanoparticles, the position and the easy magnetization axis of which are fixed but randomly distributed. Summing up the magnetic moments of the nanocrystallites inside a multicore particle, we thus obtain the magnetic moment of the multicore particle under the assumption that magnetic interactions between the nanocrystallites can be neglected. It is found that the weak-field magnetic response of these multicore particles is independent of anisotropy constant. The model is compared with recent experimental data and good agreement is found.

Libraries of Uniform Magnetic Multicore Nanoparticles with Tunable Dimensions for Biomedical and Photonic Applications.

Multicore iron oxide nanoparticles, also known as colloidal nanocrystal clusters, are magnetic materials with diverse applications in biomedicine and photonics. Here, we examine how both of their characteristic dimensional features, the primary particle and sub-micron colloid diameters, influence their magnetic properties and performance in two different applications. The characterization of these basic size-dependent properties is enabled by a synthetic strategy that provides independent control over both the primary nanocrystal and cluster dimensions. Over a wide range of conditions, electron microscopy and X-ray diffraction reveal that the oriented attachment of smaller nanocrystals results in their crystallographic alignment throughout the entire superstructure. We apply a sulfonated polymer with high charge density to prevent cluster aggregation and conjugate molecular dyes to particle surfaces so as to visualize their collection using handheld magnets. These libraries of colloidal clusters, indexed both by primary nanocrystal dimension (dp) and overall cluster diameter (Dc), form magnetic photonic crystals with relatively weak size-dependent properties. In contrast, their performance as MRI T2 contrast agents is highly sensitive to cluster diameter, not primary particle size, and is optimized for materials of 50 nm diameter (r2 = 364 mM-1 s-1). These results exemplify the relevance of dimensional control in developing applications for these versatile materials.

Features of magnetorheology of biocompatible chain-forming ferrofluids with multi-core magnetic nanoparticles: Experiment and simulation

We study the magnetorheological properties and structural transitions in novel aqueous colloidal suspensions of magnetic nanoparticles developed for biomedical applications. Defined-shape field-tunable superparamagnetic nanoparticles with clustered cores and their suspensions are produced. The region of intermediate magnetic coupling strength between colloidal ferrofluids and magnetorheological suspensions is systematically studied for the first time. Hybrid numerical simulations with hydrodynamic interactions provide full structural information. The distinctive features of the rheograms are related to transitions between Brownian and persistent microstructure, shape anisotropy, confinement and formation of magnetically coupled gel as a function of relative ratio between thermal, magnetic and hydrodynamic stresses. Non-trivial yielding scenario is observed via the shear banded (delaminated) phase, which may be more widespread in magnetic suspensions than previously thought. Analysis in terms of dimensionless parameters shows generalized behavior, which is applicable to a broad class of magnetic colloids and suspensions.

Magnetic field dependence of the effective magnetic moment of multi-core nanoparticles

The magnetic moment of magnetic nanoparticles (MNPs) is one of the key parameters for various applications. We have experimentally studied the effective magnetic moment of multi-core MNPs and especially their dependence on the applied magnetic field. In contrast to single-core MNPs, the situation is considerably more complex since the effective magnetic moment depends on the size of individual crystallites, their packing density, core configuration, and, thus, the interaction between them. Different approaches to determine the effective magnetic moment are applied for two multi-core MNP systems (FeraSpin XL and BNF Starch). The effective magnetic moment at low magnetic fields is obtained from the ac susceptibility spectra measured at ac field amplitudes up to 9 mT. The obtained values are compared with the high-field values measured at 7 T. In the small-field range (up to 9 mT), a linear field dependence of the effective magnetic moment is found for FeraSpin XL while the value of BNF Starch was found to be nearly constant. The low-field values of both MNP systems are smaller than the values at larger fields, proving the magnetic field dependence of the effective magnetic moment of multi-core MNPs. The estimated values are discussed within a simple model. A consistent picture was found for BNF Starch while the model fails for FeraSpin XL. The different behaviors of both studied multi-core MNP systems are related to the magnetic interactions between the individual crystallites inside a multi-core structure, which are strong for FeraSpin XL due to the high packing density of the crystallites.

Relating magnetization, structure and rheology in ferrofluids with multi-core magnetic nanoparticles

Due to their magnetic moments solubilized magnetic nanoparticles are able to spontaneously assemble into dipolar mesostructures, which affect the flow behavior. Multi-core magnetic nanoparticles developed for biomedical applications have enhanced magnetic properties and show significant magnetoviscous effect, but the quantitative interpretation of this phenomenon is incomplete. We apply rheological measurements, magnetic granulometry and dimensional scaling to show the existence of a master curve for magnetorheology of these materials. Using the developed approach the magnetoviscous effect can now be interpreted in a unified way within the stochastic chain model.

Biodegradable magnetic microspheres for drug targeting, temperature controlled drug release, and hyperthermia

Abstract Magnetic microspheres (MMS) used for magnetic drug targeting consist of magnetic nanoparticles (MNP) and a pharmaceutical agent embedded in a polymeric matrix material. The application of MNP for drug targeting enables guiding the MMS to a target area, imaging the position of the MMS with magnetic particle imaging, and finally inducing drug release. As latter takes place by degradation of the MMS or diffusion through the matrix, an increase in temperature, e.g. through magnetic hyperthermia, leads to an accelerated drug release. Here, MMS consisting of poly(lactic-coglycolic) acid (PLGA) with different monomer ratios were prepared by an oil-in-water emulsion evaporation method. The model drug Camptothecin (CPT) and magnetic multicore nanoparticles (MCNP) with a high specific heating rate were embedded into the microspheres. We obtained MMS in the preferred size range of 1 to 2 μm with a concentration of MCNP of 16wt%, a drug load of about 0.5wt% and an excellent heating performance of 161 W/gMMS. Investigations of the drug release behaviour showed an accelerated drug release when increasing the temperature from 20 °C to 37 °C or 43 °C by using a water bath. In addition, an increase in drug release of about 50% through magnetic heating of the MMS up to 44 °C compared to 37 °C was observed. By this, a magnetic hyperthermia induced CPT release from PLGA MMS is demonstrated for the very first time.

High intrinsic loss power of multicore magnetic nanoparticles with blood-pooling property for hyperthermia

Magnetic hyperthermia is a promising application of magnetic nanoparticles (MNPs) in cancer therapy. It is important to consider and optimize the parameters that affect heat dissipation, such as particle diameters, structures, and surface coatings. In this study, we measured the magnetic properties of two superparamagnetic nanoparticles under DC and AC magnetic fields. Resovist is approved to be used as a magnetic resonance imaging contrast agent. CMEADM-033-02, with the blood-pooling property and biocompatibility, exhibits high magnetization. The blood-pooling property makes it easier for MNPs to accumulate in tumors and tissue. While preparing samples, we aligned the easy axis of the samples using a DC magnetic field to enhance heat dissipation. We discussed the magnetic property in terms of magnetic relaxation associated with anisotropy energy. We observed that the peak frequency of Néel relaxation was considerably shifted owing to effectively changed anisotropy by the alignment of the easy axis. However, the change in the peak frequency of Néel relaxation could not be directly confirmed. Furthermore, we calculated the intrinsic loss power (ILP) and specific loss power (SLP) for heat dissipation from the areas of AC magnetization curves and estimated the SLP at 1 MHz to compare with the high heating characteristic of ILP that has been reported in a conventional study. We achieved equivalent ILP for heat dissipation as that reported in the study by aligning the easy axis of the MNPs with the blood-pooling property under a therapeutic condition.