Magnetic Hyperthermia Agents Research Articles

Synthesis and Characterization of Magnetic Composite Theragnostics by Nano Spray Drying.

Composites of magnetite nanoparticles encapsulated with polymers attract interest for many applications, especially as theragnostic agents for magnetic hyperthermia, drug delivery, and magnetic resonance imaging. In this work, magnetite nanoparticles were synthesized by coprecipitation and encapsulated with different polymers (Eudragit S100, Pluronic F68, Maltodextrin, and surfactants) by nano spray drying technique, which can produce powders of nanoparticles from solutions or suspensions. Transmission and scanning electron microscopy images showed that the bare magnetite nanoparticles have 10.5 nm, and after encapsulation, the particles have approximately 1 μm, with size and shape depending on the material’s composition. The values of magnetic saturation by SQUID magnetometry and mass residues by thermogravimetric analysis were used to characterize the magnetic content in the materials, related to their magnetite/polymer ratios. Zero-field-cooling and field-cooling (ZFC/FC) measurements showed how blocking temperatures of the powders of the composites are lower than that of bare magnetite, possibly due to lower magnetic coupling, being an interesting system to study magnetic interactions of nanoparticles. Furthermore, studies of cytotoxic effect, hydrodynamic size, and heating capacity for hyperthermia (according to the application of an alternate magnetic field) show that these composites could be applied as a theragnostic material for a non-invasive administration such as nasal.

Advantages and Disadvantages of Using Magnetic Nanoparticles for the Treatment of Complicated Ocular Disorders.

Nanomaterials provide enormous opportunities to overcome the limitations of conventional ocular delivery systems, such as low therapeutic efficacy, side effects due to the systemic exposure, or invasive surgery. Apart from the more common ocular disorders, there are some genetic diseases, such as cystic fibrosis, that develop ocular disorders as secondary effects as long as the disease progresses. These patients are more difficult to be pharmacologically treated using conventional drug routes (topically, systemic), since specific pharmacological formulations can be incompatible, display increased toxicity, or their therapeutic efficacy decreases with the administration of different kind of chemical molecules. Magnetic nanoparticles can be used as potent drug carriers and magnetic hyperthermia agents due to their response to an external magnetic field. Drugs can be concentrated in the target point, limiting the damage to other tissues. The other advantage of these magnetic nanoparticles is that they can act as magnetic resonance imaging agents, allowing the detection of the exact location of the disease. However, there are some drawbacks related to their use in drug delivery, such as the limitation to maintain efficacy in the target organ once the magnetic field is removed from outside. Another disadvantage is the difficulty in maintaining the therapeutic action in three dimensions inside the human body. This review summarizes all the application possibilities related to magnetic nanoparticles in ocular diseases.

Calcium Phosphate-Based Bioceramics in the Treatment of Osteosarcoma: Drug Delivery Composites and Magnetic Hyperthermia Agents.

The use of biomaterials in medicine is not recent, and in the last few decades, the research and development of biocompatible materials had emerged. Hydroxyapatite (HAp), a calcium phosphate that constitutes a large part of the inorganic composition of human bones and teeth, has been used as an interesting bioceramic material. Among its applications, HAp has been used to carry antitumor drugs, such as doxorubicin, cisplatin, and gemcitabine. Such HAp-based composites have an essential role in anticancer drug delivery systems, including the treatment of osteosarcoma. In addition, the association of this bioceramic with magnetic nanoparticles (MNPs) has also been used as an effective agent of local magnetic hyperthermia. Further, the combined approach of the aforementioned techniques (HAp scaffolds combined with anti-tumor drugs and MNPs) is also an attractive therapeutical alternative. Considering the promising role of the use of bioceramics in modern medicine, we proposed this review, presenting an updated perspective on the use of HAp in the treatment of cancer, especially osteosarcoma. Finally, after giving the current progress in this field, we highlight the urgent need for efforts to provide a better understanding of their potential applications.

(Carboxymethyl-stevioside)-coated magnetic dots for enhanced magnetic hyperthermia and improved glioblastoma treatment

The use of different types of biomaterials as surfactant moities has a defined role in magnetic hyperthermia-mediated cancer therapy (MHCT). In this work, we present carboxymethyl-stevioside (CMS)-modified magnetic dots (MDs) as efficient magnetic hyperthermia agents for glioma therapy. The synthesized MDs with CMS biosurfactant coating exhibited significant water stability that resulted in a remarkable specific absorption rate of 209.25 W/g on application of alternating magnetic field of strength 359 kHz and 188 Oe. The MDs further demonstrated significant anti-migratory and anti-invasive effect on glioma C6 cells by inhibiting the gene expression of matrix metalloproteinases-2 and -9. The effect of immediate and long term hyperthermia treatment was then evaluated after repetitive exposure to hyperthermia, in terms of glioma cell viability, the effect of treatment on cell morphology, the cell cycle distribution and oxidative stress generation. The results obtained suggest the promising potential of CMS-modified nano-heaters for excellent magnetic hyperthermia-mediated glioma therapy.

γ-Fe2O3 nanoflowers as efficient magnetic hyperthermia and photothermal agent

Recent reports on the magnetic nanoparticles (MNPs) as an efficient and alternative photothermal agent have excited the researchers worldwide. While MNPs have been explored well for high heating performance during magnetic hyperthermia (MHT), their full potential is yet to be explored as an efficient photothermal agent. In addition, the simultaneous exposure of alternating magnetic field (for MHT) and near infrared irradiation (for photothermal therapy PTT) can drastically enhance the heating behaviour of MNPs. In the present work we explored microwave assisted polyol method to get γ-Fe2O3 nanoflowers. The use of sodium acetate in varying amounts, as an alkali source, allowed the modification of structural and magnetic properties leading to the formation of nanoflower with high heating performance during MHT and PTT. Role of defects in γ-Fe2O3 nanoflowers were investigated using photoluminescence spectroscopy which highlighted distinct role of oxygen vacancies and surface states. The nanoflowers with better crystallinity and relatively higher coercive field performed well during MHT. The observed high intrinsic loss power value of 15.21 ± 0.34 nHm2Kg-as significantly higher than the commercially available ferrofluids and previously reported values for nanoflowers. During PTT, the therapeutic temperature of 42 °C was achieved for the aqueous suspension with a concentration as low as 100 µg/mL which demonstrates the superiority of γ-Fe2O3 nanoflowers as an efficient PTT agent.

Synergistic Photothermal-Chemotherapy Based on the Use of Biomimetic Magnetic Nanoparticles.

MamC-mediated biomimetic magnetic nanoparticles (BMNPs) have emerged as one of the most promising nanomaterials due to their magnetic features (superparamagnetic character and large magnetic moment per particle), their novel surface properties determined by MamC, their biocompatibility and their ability as magnetic hyperthermia agents. However, the current clinical application of magnetic hyperthermia is limited due to the fact that, in order to be able to reach an effective temperature at the target site, relatively high nanoparticle concentration, as well as high magnetic field strength and/or AC frequency are needed. In the present study, the potential of BMNPs to increase the temperature upon irradiation of a laser beam in the near infrared, at a wavelength at which tissues become partially transparent, is explored. Moreover, our results also demonstrate the synergy between photothermia and chemotherapy in terms of drug release and cytotoxicity, by using BMNPs functionalized with doxorubicin, and the effectiveness of this combination therapy against tumor cells in in vitro experiments. Therefore, the findings of the present study open the possibility of a novel, alternative approach to fight localized tumors.

Biocompatible magnetic gelatin nanoparticles with enhanced MRI contrast performance prepared by single-step desolvation method

Magnetic nanoparticles are versatile materials that have boosted the development of different biomedical applications, being superparamagnetic magnetite nanoparticles a milestone in the field, after achieving clinical approval as contrast agents in magnetic resonance imaging (Feridex®), magnetic hyperthermia agents for oncological treatments (NanoTherm®), or iron deficiency supplement (Feraheme®). However, its potential as theragnostic agent could be further expanded by its encapsulation within a biodegradable hydrogel, capable of enhancing the biocompatibility and loading abilities, to simultaneously carry drugs, radiotracers, or biomolecules. Gelatin, is a natural biopolymer with optimal in vivo feature and gelling capacity that has been extensively used for decades in pharmaceuticals. In this work, we have addressed the preparation of gelatin nanoparticles, bare and loaded with magnetite nanoparticles, with controlled size to be used as contrast agents in magnetic resonance imaging. The main formulation parameters influencing the preparation of gelatin nanoparticles with controlled size by single-step desolvation method, were studied and optimized, to produce small gelatin nanoparticles (97nm) and highly loaded (38% w/w) Fe3O4@citrate gelatin nanoparticles (150 nm) with high magnetic response (65emus/g). The viability assays of the magnetic gelatin nanoparticles, tested with mesenchymal stem cells, showed negligible toxicity and in vitro magnetic resonance imaging tests, performed in agar phantoms, revealed a good contrast for T2 weighting MRI, r2 = 265.5(mM−1 s−1), superior to commercial products, such as Resovist or Endorem.

Antibacterial properties of ferrimagnetic and superparamagnetic nanoparticles: a comparative study

In this study, antibacterial impact of magnetic nanocomposite (MNC: MoS2/CoFe2O4) and super paramagnetic iron oxide nanoparticle (SPION: Fe3O4-Casein) against staphylococcus aureus was studied. It was expected that such comparative study, address key points in optimization of synthesis and design of nanomaterials, which are supposed to be used as antibacterial agents for magnetic fluid hyperthermia (MFH) purposes. As the results, the MNC and SPION had average sizes of 17±4 nm and 15±5 nm, and diffused homogenously in agarose gel. They both were bacteriostatic against S. aureus at very low concentrations, while were bactericidal at concentrations of 200 µg/mL and more in MFH condition. In conclusion, both MNC and SPION inhibit S. aureus viability when low amplitude (H = 31.16 mT) alternative magnetic field (AMF: f = 150 kHz) was applied. Therefore, both of the nanomaterials are eligible to be considered as antibacterial candidates for treatment of complicated infections in upper respiratory tract or skin.

Nanoparticles exhibiting self-regulating temperature as innovative agents for Magnetic Fluid Hyperthermia.

During the last few years, for therapeutic purposes in oncology, considerable attention has been focused on a method called magnetic fluid hyperthermia (MFH) based on local heating of tumor cells. In this paper, an innovative, promising nanomaterial, M48 composed of iron oxide-based phases has been tested. M48 shows self-regulating temperature due to the observable second order magnetic phase transition from ferromagnetic to paramagnetic state. A specific hydrophilic coating based on both citrate ions and glucose molecules allows high biocompatibility of the nanomaterial in biological matrices and its use in vivo. MFH mediator efficiency is demonstrated in vitro and in vivo in breast cancer cells and tumors, confirming excellent features for biomedical application. The temperature increase, up to the Curie temperature, gives rise to a phase transition from ferromagnetic to paramagnetic state, promoting a shortage of the r2 transversal relaxivity that allows a switch in the contrast in Magnetic Resonance Imaging (MRI). Combining this feature with a competitive high transversal (spin-spin) relaxivity, M48 paves the way for a new class of temperature sensitive T2 relaxing contrast agents. Overall, the results obtained in this study prepare for a more affordable and tunable heating mechanism preventing the damages of the surrounding healthy tissues and, at the same time, allowing monitoring of the temperature reached.

Recent Insights into the Potential of Magnetic Metal Nanostructures as Magnetic Hyperthermia Agents

The advancements in magnetic nanoparticle mediated hyperthermia give so many optimistic and fruitful results that make it a promising and complementary approach for the existing treatment modalities of cancer. This thermotherapy is gaining wide acceptance among the medical community compared to the conventional treatment methods. The former provides a local heat generation in the malignant tumor cells and remains non-invasive to the adjacent healthy cells. The increased heating efficiency of magnetic nanoparticles and the control of local therapeutic temperature are the main challenges of hyperthermia. Superparamagnetic Iron Oxide nanoparticles have been intensively studied and dominating in magnetic hyperthermia. Recently many researchers successfully demonstrated high heating efficiency and biocompatibility of a wide variety of magnetic metal nanoparticles and proposed as the most promising alternative for traditional iron oxides, which opens up a new avenue for magnetic metal nanoparticles in magnetic hyperthermia. The review presents the recent advancements that occurred in the field of metal nanoparticle mediated magnetic hyperthermia. The theory underlying heat generation, synthesis methods, biofunctionalization, Specific Absorption Rate studies, challenges and future perspectives of magnetic metal nanoparticles are presented. This will inspire more in-depth research and advance practical applications of metal nanoparticles in magnetic hyperthermia.

Simple Sonochemical Method to Optimize the Heating Efficiency of Magnetic Nanoparticles for Magnetic Fluid Hyperthermia.

We developed a fast, single-step sonochemical strategy for the green manufacturing of magnetite (Fe3O4) magnetic nanoparticles (MNPs), using iron sulfate (FeSO4) as the sole source of iron and sodium hydroxide (Na(OH)) as the reducing agent in an aqueous medium. The designed methodology reduces the environmental impact of toxic chemical compounds and minimizes the infrastructure requirements and reaction times down to minutes. The Na(OH) concentration has been varied to optimize the final size and magnetic properties of the MNPs and to minimize the amount of corrosive byproducts of the reaction. The change in the starting FeSO4 concentration (from 5.4 to 43.1 mM) changed the particle sizes from (20 ± 3) to (58 ± 8) nm. These magnetite MNPs are promising for biomedical applications due to their negative surface charge, good heating properties (≈324 ± 2 W/g), and low cytotoxic effects. These results indicate the potential of this controlled, easy, and rapid ultrasonic irradiation method to prepare nanomaterials with enhanced properties and good potential for use as magnetic hyperthermia agents.

Exploiting Unique Alignment of Cobalt Ferrite Nanoparticles, Mild Hyperthermia, and Controlled Intrinsic Cobalt Toxicity for Cancer Therapy.

Nanoparticle-based magnetic hyperthermia is a well-known thermal therapy platform studied to treat solid tumors, but its use for monotherapy is limited due to incomplete tumor eradication at hyperthermia temperature (45°C).It is often combined with chemotherapy for obtaining a more effective therapeutic outcome. Cubic-shaped cobalt ferrite nanoparticles (Co-Fe NCs) serve as magnetic hyperthermia agents and as a cytotoxic agent due to the known cobalt ion toxicity, allowing the achievement of both heat and cytotoxic effects from a single platform. In addition to this advantage, Co-Fe NCs have the unique ability to form growing chains under an alternating magnetic field (AMF). This unique chain formation, along with the mild hyperthermia and intrinsic cobalt toxicity, leads to complete tumor regression and improved overall survival in an in vivo murine xenograft model, all under clinically approved AMF conditions. Numerical calculations identify magnetic anisotropy as the main Co-Fe NCs' feature to generate such chain formations. This novel combination therapy can improve the effects of magnetic hyperthermia, inaugurating investigation of mechanical behaviors of nanoparticles under AMF, as a new avenue for cancer therapy.

Nanoformulation Design Including MamC-Mediated Biomimetic Nanoparticles Allows the Simultaneous Application of Targeted Drug Delivery and Magnetic Hyperthermia.

The design of novel nanomaterials that can be used as multifunctional platforms allowing the combination of therapies is gaining increased interest. Moreover, if this nanomaterial is intended for a targeted drug delivery, the use of several guidance methods to increase guidance efficiency is also crucial. Magnetic nanoparticles (MNPs) allow this combination of therapies and guidance strategies. In fact, MNPs can be used simultaneously as drug nanocarriers and magnetic hyperthermia agents and, moreover, they can be guided toward the target by an external magnetic field and by their functionalization with a specific probe. However, it is difficult to find a system based on MNPs that exhibits optimal conditions as a drug nanocarrier and as a magnetic hyperthermia agent. In this work, a novel nanoformulation is proposed to be used as a multifunctional platform that also allows dual complementary guidance. This nanoformulation is based on mixtures of inorganic magnetic nanoparticles (M) that have been shown to be optimal hyperthermia agents, and biomimetic magnetic nanoparticles (BM), that have been shown to be highly efficient drug nanocarriers. The presence of the magnetosome protein MamC at the surface of BM confers novel surface properties that allow for the efficient and stable functionalization of these nanoparticles without the need of further coating, with the release of the relevant molecule being pH-dependent, improved by magnetic hyperthermia. The BM are functionalized with Doxorubicin (DOXO) as a model drug and with an antibody that allows for dual guidance based on a magnetic field and on an antibody. The present study represents a proof of concept to optimize the nanoformulation composition in order to provide the best performance in terms of the magnetic hyperthermia agent and drug nanocarrier.

Tunable Fe3O4 Nanorods for Enhanced Magnetic Hyperthermia Performance

Magnetic hyperthermia is one of the most promising techniques for treating gynecological cancer, where magnetite (Fe3O4) is the most common nanomaterial used as a magnetic hyperthermia agent. Here, we demonstrate that optimal Fe3O4 nanorods (NRs) can act as a magnetic hyperthermia agent with higher specific absorption rate (SAR), which is mostly attributed to their enhanced surface anisotropy. As a result, Fe3O4 NRs could effectively hinder the growth of gynecological cancer cells in nude mice models, again demonstrating its good magnetic heating properties. These results provide a powerful basis for the development of an ideal magnetic hyperthermia agent with enhanced SAR, thereby effectively treating gynecological cancer in clinical practice.

Bi-Magnetic Core-Shell CoFe2O4@MnFe2O4 Nanoparticles for In Vivo Theranostics.

In this work, we report the synthesis and characterization of three magnetic nanosystems, CoFe2O4, CoFe2O4@ZnFe2O4, and CoFe2O4@MnFe2O4, which were developed as potential theranostic agents for magnetic hyperthermia and magnetic resonance imaging (MRI). These nanosystems have been thoroughly characterized by X-ray Diffraction (XRD), Transmission Electron Miscroscopy (TEM), Dark Field-TEM (DF-TEM), Vibrating Sample Magnetometry (VSM), and inductive heating, in order to elucidate their structure, morphology, and magnetic properties. The bi-magnetic CoFe2O4@ZnFe2O4 and CoFe2O4@MnFe2O4 nanoparticles (NPs) exhibited a core-shell structure with a mean average particle size of 11.2 ± 1.4 nm and 14.4 ± 2.4 nm, respectively. The CoFe2O4@MnFe2O4 NPs showed the highest specific absorption rate (SAR) values (210–320 W/g) upon exposure to an external magnetic field, along with the highest saturation magnetization (Ms). Therefore, they were selected for functionalization with the PEGylated ligand to make them stable in aqueous media. After the functionalization process, the NPs showed high magnetic relaxivity values and very low cytotoxicity, demonstrating that CoFe2O4@MnFe2O4 is a good candidate for in vivo applications. Finally, in vivo MRI experiments showed that PEGylated CoFe2O4@MnFe2O4 NPs produce high T2 contrast and exhibit very good stealth properties, leading to the efficient evasion of the mononuclear phagocyte system. Thus, these bi-magnetic core-shell NPs show great potential as theranostic agents for in vivo applications, combining magnetic hyperthermia capabilities with high MRI contrast.

Cobalt ferrite nanoparticles for bimodal hyperthermia and their mechanistic interactions with lysozyme

Magnetic nanoparticles find several applications in cancer therapy. We have synthesized cobalt ferrite nanoparticles (CFNPs) and evaluated them as agents for magnetic hyperthermia (MH) effect. The CFNPs were well characterized for size and morphology using TEM, FESEM, and DLS. They were in the size range 8–25 nm with a roughly spherical shape. They were ferrimagnetic with a saturation magnetization of 42 emu/g. They showed a temperature increase of 38 °C when exposed to an alternating magnetic field, and also showed photothermal effect. These two modes of heating along with magnetic targeting make these CFNPs a suitable candidate for biomedical applications. Their interaction with the protein lysozyme was also investigated. UV/visible and fluorescence spectroscopy showed that the CFNPs bind strongly to the protein with the binding constant of the order 105. Time-resolved fluorescence studies validated binding between them. CD spectroscopy showed that protein's conformation changed upon binding to CFNPs with a decrease in the percentage of α-helix. Molecular docking studies were performed to find out the site of binding in the protein.

Continuous production of magnetic iron oxide nanocrystals by oxidative precipitation

Abstract Continuous processes are always preferred over batch ones when reproducible and scalable industrial procedures are needed. This work illustrates the production of magnetite nanoparticles by oxidative precipitation in aqueous media, following a continuous approach that offers additional advantages. Particularly, the developed reaction setup succeeds (i) the complete separation of the green rust’s precipitation from Fe3O4 nucleation, (ii) the achievement of constant concentrations in all ionic and solid forms throughout the production line when steady-state is reached, what means constant supersaturation from both the formation of green rust and Fe3O4, and (iii) the possibility to control critical parameters, such as OH− excess over the initial stoichiometric Fe(OH)2 precipitation, through on-line regulation of synthesis parameters such as the reactor’s pH and redox potential. Importantly, continuous flow synthesis of Fe3O4 nanoparticles enables high production capacities, low energy consumption and proportional scale-up at any volume. As a proof of concept, obtained nanoparticles were evaluated according to their magnetic response as potential magnetic hyperthermia agents indicating significant improvement of heating efficiency that goes up to 1.5–2 kW/gFe3O4 for both smaller (~40 nm) and larger (~200 nm) particles.

The cell uptake properties and hyperthermia performance of Zn0.5Fe2.5O4/SiO2 nanoparticles as magnetic hyperthermia agents.

Zn0.5Fe2.5O4 nanoparticles (NPs) of 22 nm are synthesized by a one-pot approach and coated with silica for magnetic hyperthermia agents. The NPs exhibit superparamagnetic characteristics, high-specific absorption rate (SAR) (1083 wg−1, f = 430 kHz, H = 27 kAm−1), large saturation magnetization (Ms = 85 emu g−1), excellent colloidal stability and low cytotoxicity. The cell uptake properties have been investigated by Prussian blue staining, transmission electron microscopy and the inductively coupled plasma-mass spectrometer, which resulted in time-dependent and concentration-dependent internalization. The internalization appeared between 0.5 and 2 h, the NPs were mainly located in the lysosomes and kept in good dispersion after incubation with human osteosarcoma MG-63 cells. Then, the relationship between cell uptake and magnetic hyperthermia performance was studied. Our results show that the hyperthermia efficiency was related to the amount of internalized NPs in the tumour cells, which was dependent on the concentration and incubation time. Interestingly, the NPs could still induce tumour cells to apoptosis/necrosis when extracellular NPs were rinsed, but the cell kill efficiency was lower than that of any rinse group, which indicated that local temperature rise was the main factor that induced tumour cells to death. Our findings suggest that this high SAR and biocompatible silica-coated Zn0.5Fe2.O4 NPs could serve as new agents for magnetic hyperthermia.

Magnetic Fe3O4@PVP nanotubes with high heating efficiency for MRI-guided magnetic hyperthermia applications

The Fe3O4@PVP nanotubes have been successfully synthesized in large quantities using a hydrothermal synthesis. The fabricated sample shows a relatively high transverse relaxivity of 97.97 mM−1 s−1 for magnetic resonance imaging (MRI) and a high heating efficiency of 5050 W/g for magnetic hyperthermia. The results suggest that the fabricated samples hold a great potential for the MRI-guided magnetic hyperthermia applications in the cancer theranostic fields. In addition, this study also opens the window to explore high efficiency magnetic hyperthermia agents by controlling the shape of the magnetic nanostructures.

Synthesis and Characterization of CeGdZn-Ferrite Nanoparticles as Magnetic Hyperthermia Application Agents

This study focuses on the synthesis and characterization of a magnetic nanomaterial used in magnetic hyperthermia. Cerium gadolinium zinc-iron (CeGdZnFe) magnetic nanoparticles were synthesized by a coprecipitation method for application as magnetic hyperthermia agents. Determination of phase purity and their identification was achieved by X-ray diffraction studies using a Phillips powder diffractometer with Cu Kα radiation. Typical TEM micrographs of the dispersion of CeGdZn-ferrite nanoparticles and CeGdZn-ferrite PEG-encapsulated nanoparticles in ethanol deposited over a Cu grid were taken as part of the characterization techniques to be used for newly developed materials. It was then fitted by a Gaussian distribution with mean diameter dm ±1.0 nm. The investigation of magnetic properties showed that adjusting, Gd and Zn contributes to the nanoparticles added to the adjustment of all magnetic properties of CeGdZnFe.