The relevance of Brownian relaxation as power absorption mechanism in Magnetic Hyperthermia.
ABSTRACT: The Linear Response Theory (LRT) is a widely accepted framework to analyze the power absorption of magnetic nanoparticles for magnetic fluid hyperthermia. Its validity is restricted to low applied fields and/or to highly anisotropic magnetic nanoparticles. Here, we present a systematic experimental analysis and numerical calculations of the specific power absorption for highly anisotropic cobalt ferrite (CoFe2O4) magnetic nanoparticles with different average sizes and in different viscous media. The predominance of Brownian relaxation as the origin of the magnetic losses in these particles is established, and the changes of the Specific Power Absorption (SPA) with the viscosity of the carrier liquid are consistent with the LRT approximation. The impact of viscosity on SPA is relevant for the design of MNPs to heat the intracellular medium during in vitro and in vivo experiments. The combined numerical and experimental analyses presented here shed light on the underlying mechanisms that make highly anisotropic MNPs unsuitable for magnetic hyperthermia.
Project description:This work aims to demonstrate the need for in silico design via numerical simulation to produce optimal Fe<sub>3</sub>O<sub>4</sub>-based magnetic nanoparticles (MNPs) for magnetic hyperthermia by minimizing the impact of intracellular environments on heating efficiency. By including the relevant magnetic parameters, such as magnetic anisotropy and dipolar interactions, into a numerical model, the heating efficiency of as prepared colloids was preserved in the intracellular environment, providing the largest in vitro specific power absorption (SPA) values yet reported. Dipolar interactions due to intracellular agglomeration, which are included in the simulated SPA, were found to be the main cause of changes in the magnetic relaxation dynamics of MNPs under in vitro conditions. These results pave the way for the magnetism-based design of MNPs that can retain their heating efficiency in vivo, thereby improving the outcome of clinical hyperthermia experiments.
Project description:We present evidence on the effects of exogenous heating by water bath (WB) and magnetic hyperthermia (MHT) on a glial micro-tumor phantom. To this, magnetic nanoparticles (MNPs) of 30-40?nm were designed to obtain particle sizes for maximum heating efficiency. The specific power absorption (SPA) values (f?=?560?kHz, H?=?23.9?kA/m) for as prepared colloids (533-605?W/g) dropped to 98-279?W/g in culture medium. The analysis of the intracellular MNPs distribution showed vesicle-trapped MNPs agglomerates spread along the cytoplasm, as well as large (~0.5-0.9??m) clusters attached to the cell membrane. Immediately after WB and MHT (T?=?46?°C for 30?min) the cell viability was ?70% and, after 4.5?h, decreased to 20-25%, demonstrating that metabolic processes are involved in cell killing. The analysis of the cell structures after MHT revealed a significant damage of the cell membrane that is correlated to the location of MNPs clusters, while local cell damage were less noticeable after WB without MNPs. In spite of the similar thermal effects of WB and MHT on the cell viability, our results suggest that there is an additional mechanism of cell damage related to the presence of MNPs at the intracellular space.
Project description:A well-established method for treating cancerous tumors is magnetic hyperthermia, which uses localized heat generated by the relaxation mechanism of magnetic nanoparticles (MNPs) in a high-frequency alternating magnetic field. In this work, we investigate the heating efficiency of cylindrical NiFe MNPs, fabricated by template-assisted pulsed electrodeposition combined with differential chemical etching. The cylindrical geometry of the MNP enables the formation of the triple vortex state, which increases the heat generation efficiency by four times. Using time-dependent calorimetric measurements, the specific absorption rate (SAR) of the MNPs was determined and compared with the numerical calculations from micromagnetic simulations and vibrating sample magnetometer measurements. The magnetization reversal of high aspect ratios MNPs showed higher remanent magnetization and low-field susceptibility leading to higher hysteresis losses, which was reflected in higher experimental and theoretical SAR values. The SAR dependence on magnetic field strength exhibited small SAR values at low magnetic fields and saturates at high magnetic fields, which is correlated to the coercive field of the MNPs and a characteristic feature of ferromagnetic MNPs. The optimization of cylindrical NiFe MNPs will play a pivotal role in producing high heating performance and biocompatible magnetic hyperthermia agents.
Project description:Magnetic fluid hyperthermia (MFH) employs heat dissipation from magnetic nanoparticles to elicit a therapeutic outcome in tumor sites, which results in either cell death (>42 °C) or damage (<42 °C) depending on the localized rise in temperature. We investigated the therapeutic effect of MFH in immortalized T lymphocyte (Jurkat) cells using monodisperse magnetite (Fe(3)O(4)) nanoparticles (MNPs) synthesized in organic solvents and subsequently transferred to aqueous phase using a biocompatible amphiphilic polymer. Monodisperse MNPs, ∼16 nm diameter, show maximum heating efficiency, or specific loss power (watts/g Fe(3)O(4)) in a 373 kHz alternating magnetic field. Our in vitro results, for 15 min of heating, show that only 40% of cells survive for a relatively low dose (490 μg Fe/ml) of these size-optimized MNPs, compared to 80% and 90% survival fraction for 12 and 13 nm MNPs at 600 μg Fe/ml. The significant decrease in cell viability due to MNP-induced hyperthermia from only size-optimized nanoparticles demonstrates the central idea of tailoring size for a specific frequency in order to intrinsically improve the therapeutic potency of MFH by optimizing both dose and time of application.
Project description:The two major limitations for nanoparticle based magnetic hyperthermia in theranostics are the delivery of a sufficient number of magnetic nanoparticles (MNPs) with high heating power to specific target cells and the residence time of the MNPs at the target location. Ferromagnetic or Ferrimagnetic single domain nanoparticles (F-MNPs), with a permanent magnetic dipole, produce larger magnetic and thermal responses than superparamagnetic nanoparticles (SP-MNPs) but also agglomerate more. MNP agglomeration degrades their heating potential due to dipolar interaction effects and interferes with specific targeting. Additionally, MNPs bound to cells are often endocytosed by the cells or, in vivo, cleared out by the immune system via uptake in macrophages. Here, we present a versatile approach to engineer inorganic-polymeric microdisks, loaded with biomolecules, fluorophores and Fe3O4 F-MNPs that solves both challenges. These microdisks deliver the F-MNPs efficiently, while controlling any undesirable agglomeration and dipolar interaction, while also rendering the F-MNPs endocytosis resistant. We show that these micro-devices are suitable carriers to transport a flat assembly of F-MNPs to the cell membrane unchanged, preserving the magnetic response of the MNPs in any biological environment. The F-MNPs concentration per microdisk and degree of MNP interaction are tunable. We demonstrate that the local heat generated in microdisks is proportional to the surface density of F-MNPs when attached to the cell membrane. The key innovation in the production of these microdisks is the fabrication of a mushroom-shaped photolithographic template that enables easy assembly of the inorganic film, polymeric multilayers, and MNP cargo while permitting highly efficient lift-off of the completed microdisks. During the harvesting of the flat microdisks, the supporting mushroom-shaped templates are sacrificed. These resulting magnetic hybrid microdisks are tunable and efficient devices for magnetothermal actuation and hyperthermia.
Project description:A combination of carbon ions/photons irradiation and hyperthermia as a novel therapeutic approach for the in-vitro treatment of pancreatic cancer BxPC3 cells is presented. The radiation doses used are 0-2 Gy for carbon ions and 0-7 Gy for 6 MV photons. Hyperthermia is realized via a standard heating bath, assisted by magnetic fluid hyperthermia (MFH) that utilizes magnetic nanoparticles (MNPs) exposed to an alternating magnetic field of amplitude 19.5 mTesla and frequency 109.8 kHz. Starting from 37 °C, the temperature is gradually increased and the sample is kept at 42 °C for 30 min. For MFH, MNPs with a mean diameter of 19 nm and specific absorption rate of 110 ± 30 W/gFe3o4 coated with a biocompatible ligand to ensure stability in physiological media are used. Irradiation diminishes the clonogenic survival at an extent that depends on the radiation type, and its decrease is amplified both by the MNPs cellular uptake and the hyperthermia protocol. Significant increases in DNA double-strand breaks at 6 h are observed in samples exposed to MNP uptake, treated with 0.75 Gy carbon-ion irradiation and hyperthermia. The proposed experimental protocol, based on the combination of hadron irradiation and hyperthermia, represents a first step towards an innovative clinical option for pancreatic cancer.
Project description:Efficient use of magnetic hyperthermia in clinical cancer treatment requires biocompatible magnetic nanoparticles (MNPs), with improved heating capabilities. Small (~34 nm) and large (~270 nm) Fe?O?-MNPs were synthesized by means of a polyol method in polyethylene-glycol (PEG) and ethylene-glycol (EG), respectively. They were systematically investigated by means of X-ray diffraction, transmission electron microscopy and vibration sample magnetometry. Hyperthermia measurements showed that Specific Absorption Rate (SAR) dependence on the external alternating magnetic field amplitude (up to 65 kA/m, 355 kHz) presented a sigmoidal shape, with remarkable SAR saturation values of ~1400 W/gMNP for the small monocrystalline MNPs and only 400 W/gMNP for the large polycrystalline MNPs, in water. SAR values were slightly reduced in cell culture media, but decreased one order of magnitude in highly viscous PEG1000. Toxicity assays performed on four cell lines revealed almost no toxicity for the small MNPs and a very small level of toxicity for the large MNPs, up to a concentration of 0.2 mg/mL. Cellular uptake experiments revealed that both MNPs penetrated the cells through endocytosis, in a time dependent manner and escaped the endosomes with a faster kinetics for large MNPs. Biodegradation of large MNPs inside cells involved an all-or-nothing mechanism.
Project description:This work reports important advances in the study of magnetic nanoparticles (MNPs) related to their application in different research fields such as magnetic hyperthermia. Nanotherapy based on targeted nanoparticles could become an attractive alternative to conventional oncologic treatments as it allows a local heating in tumoral surroundings without damage to healthy tissue. RGD-peptide-conjugated MNPs have been designed to specifically target ?<sub>V</sub>?<sub>3</sub> receptor-expressing cancer cells, being bound the RGD peptides by "click chemistry" due to its selectivity and applicability. The thermal decomposition of iron metallo-organic precursors yield homogeneous Fe<sub>3</sub>O<sub>4</sub> nanoparticles that have been properly functionalized with RGD peptides, and the preparation of magnetic fluids has been achieved. The nanoparticles were characterized by transmission electron microscopy (TEM), vibrating sample magnetometry (VSM), electron magnetic resonance (EMR) spectroscopy and magnetic hyperthermia. The nanoparticles present superparamagnetic behavior with very high magnetization values, which yield hyperthermia values above 500 W/g for magnetic fluids. These fluids have been administrated to rats, but instead of injecting MNP fluid directly into liver tumors, intravascular administration of MNPs in animals with induced colorectal tumors has been performed. Afterwards the animals were exposed to an alternating magnetic field in order to achieve hyperthermia. The evolution of an in vivo model has been described, resulting in a significant reduction in tumor viability.
Project description:Magnetic nanoparticles (MNPs) have been extensively used in drug/gene delivery, hyperthermia therapy, magnetic particle imaging (MPI), magnetic resonance imaging (MRI), magnetic bioassays, and so forth. With proper surface chemical modifications, physicochemically stable and nontoxic MNPs are emerging contrast agents and tracers for in vivo MRI and MPI applications. Herein, we report the high magnetic moment, irregularly shaped ?'-Fe4N nanoparticles for enhanced hyperthermia therapy and T2 contrast agent for MRI application. The static and dynamic magnetic properties of ?'-Fe4N nanoparticles are characterized by a vibrating sample magnetometer (VSM) and a magnetic particle spectroscopy (MPS) system, respectively. Compared to the ?-Fe2O3 nanoparticles, ?'-Fe4N nanoparticles show at least three times higher saturation magnetization, which, as a result, gives rise to the stronger dynamic magnetic responses as proved in the MPS measurement results. In addition, ?'-Fe4N nanoparticles are functionalized with an oleic acid layer by a wet mechanical milling process. The morphologies of as-milled nanoparticles are characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), and nanoparticle tracking analyzer (NTA). We report that with proper surface chemical modification and tuning on morphologies, ?'-Fe4N nanoparticles could be used as tiny heating sources for hyperthermia and contrast agents for MRI applications with minimum dose.
Project description:A method based on the thermodynamic equilibrium reached between the hybridization and denaturation of double-stranded DNA (ds-DNA) is opened up to evaluate the hyperthermia performance of magnetic nanoparticles (MNPs). Two kinds of MNPs with different sizes and magnetic performance are chosen, and their temperature increments at the surface area under an alternating magnetic field (AMF) are calculated and compared through the concentration variation of ds-DNA modified on the surface. The temperature difference between the surface area of MNPs and bulk solution is also investigated, which can reach as high as 57.8°C when AMF applied for 300?s. This method provides a direct path way of comparison hyperthermia ability of MNPs, and serves as a good reference to choose MNPs and decides the therapy parameters based on the unique drug response of individual patient.