Nowadays, magnetic hyperthermia constitutes a complementary approach to cancer treatment. The use of magnetic particles as heating mediators, proposed in the 1950s, provides a novel strategy for improving tumor treatment and, consequently, patient quality of life. This review reports a broad overview about several aspects of magnetic hyperthermia addressing new perspectives and the progress on relevant features such as the ad hoc preparation of magnetic nanoparticles, physical modeling of magnetic heating, methods to determine the heat dissipation power of magnetic colloids including the development of experimental apparatus and the influence of biological matrices on the heating efficiency.Comment: 104 pages, 28 figures. Manuscript accepted for publication in Applied Physics Review

Despite magnetic hyperthermia being considered one of the most promising techniques for cancer treatment, until now spherical magnetite (Fe 3 O 4 ) or maghemite (γ-Fe 2 O 3 ) nanoparticles, which are the most commonly employed and only FDA approved materials, yield the limited heating capacity. Therefore, there is an increasing need for new strategies to improve the heating efficiency or the specific absorption rate (SAR) of these nanosystems. Recently, a large improvement in SAR has been reported for nanocubes of Fe 3 O 4 relative to their spherical counterpart, as a result of their enhanced surface anisotropy and chainlike particle formation. Considering the proven advantages of high aspect ratio onedimensional (1D) Fe 3 O 4 nanostructures over their spherical and cubic counterparts, such as larger surface area, multisegmented capabilities, enhanced blood circulation time, and prolonged retention in tumors, we propose a novel approach that utilizes this 1D nanostructure for enhanced hyperthermia. Here, we demonstrate that the SAR of iron oxide nanostructures can be enhanced and tuned by altering their aspect ratio. Calorimetric and ac magnetometry experiments performed for the first time on highly crystalline Fe 3 O 4 nanorods consistently show large SAR values (862 W/g for an ac field of 800 Oe), which are superior to spherical and cubic nanoparticles of similar volume (∼140 and ∼314 W/g, respectively). Increasing the aspect ratio of the nanorods from 6 to 11 improves the SAR by 1.5 times. The nanorods are rapidly aligned by the applied ac field, which appreciably increases the SAR values. A detailed analysis of the effect of the alignment of the nanorods in agar indicates an appreciable SAR increase up to 30% when the nanorods are parallel to the field. These findings pave a new pathway for the design of novel high-aspect ratio magnetic nanostructures for advanced hyperthermia.

Magnetic nanoparticle-mediated hyperthermia is a very promising therapy for cancer treatment. In this field, superparamagnetic iron oxide nanoparticles have been commonly employed because of their intrinsic biocompatibility, but they present some limitations that restrict their heating efficiency (specific absorption rate, SAR). Therefore, we have investigated how tuning the size and shape of these iron oxide nanoparticles can be useful to enhance their hyperthermia responses. Monodisperse and crystalline iron oxide nanoparticles have been synthesized by thermal decomposition in two different shapes (spheres and cubes) in a wide range of sizes, ∼10–100 nm. We have thoroughly characterized them both structurally (X-ray diffraction and transmission electron microscopy) and magnetically (physical property measurement system), and then we have analyzed their heating efficiency using a combination of calorimetric and AC magnetometry measurements (0–800 Oe, 300 kHz). We have been able to delimit a range of optimum sizes to maximize the heating efficiency of these nanoparticles depending on their shape. We find that the nanospheres exhibit the highest heating efficiency for sizes around 30–50 nm, while the nanocubes show a sharp increase in the heating efficiency around 30–35 nm. The SAR variation has been related to the magnetic anisotropy of the nanoparticles that depends on their size, shape, arrangement, and dipolar interactions.

Magnetic hyperthermia treatment requires biocompatible magnetic nanoparticles with improved heating capacities to become a viable clinical method for cancer treatment. Although small superparamagnetic iron oxide nanoparticles under low fields have been favored (linear response theory regime), these nanoparticles present a series of limitations, including relatively low heating efficiency (specific absorption rate or SAR), that need to be overcome to make magnetic hyperthermia an efficient clinical application. We here show that by modifying the shape into deformed cubes (octopods) and tuning their size, their SAR can be greatly increased up to 70% (from 140 to 240 W/g). By using nonhydrolytic thermal decomposition, we have obtained highly crystalline monodisperse nano-octopods for different sizes (17–47 nm), and their heating response has been extensively studied in a wide range of AC fields (20–800 Oe) using combined calorimetric and AC magnetometry experiments. Our results consistently reveal that at AC fields (≤300–400 Oe), the nano-octopods with the smallest size (17 nm) possessed the largest SAR, but for higher AC fields (>400 Oe) the SAR tended to increase with increasing particle size, reaching maximum values up to 415 W/g for the 47 nm octopods. The different response has been attributed to the ratio between the applied field and the anisotropy field, which activates different heating mechanisms: mainly related to viscous losses in the case of the smallest nano-octopods, while mostly attributed to hysteresis losses in the case of the biggest ones. Our study provides important insights into the size-dependent SAR in anisotropic nanoparticles, other than what has been predicted by the linear response theory for the case of spherical nanoparticles, and paves a new pathway for the design and synthesis of novel anisotropic iron oxide nanostructures with optimal heating efficiency for enhanced hyperthermia.

Magnetotactic bacteria are aquatic microorganisms that internally biomineralize chains of magnetic nanoparticles (called magnetosomes) and use them as a compass. Here it is shown that magnetotactic bacteria of the strain Magnetospirillum gryphiswaldense present high potential as magnetic hyperthermia agents for cancer treatment. Their heating efficiency or specific absorption rate is determined using both calorimetric and AC magnetometry methods at different magnetic field amplitudes and frequencies. In addition, the effect of the alignment of the bacteria in the direction of the field during the hyperthermia experiments is also investigated. The experimental results demonstrate that the biological structure of the magnetosome chain of magnetotactic bacteria is perfect to enhance the hyperthermia efficiency. Furthermore, fluorescence and electron microscopy images show that these bacteria can be internalized by human lung carcinoma cells A549, and cytotoxicity studies reveal that they do not affect the viability or growth of the cancer cells. A preliminary in vitro hyperthermia study, working on clinical conditions, reveals that cancer cell proliferation is strongly affected by the hyperthermia treatment, making these bacteria promising candidates for biomedical applications.

Over the past two decades, magnetic hyperthermia and photothermal therapy are becoming very promising supplementary techniques to well-established cancer treatments such as radiotherapy and chemotherapy. These techniques have dramatically improved their ability to perform controlled treatments, relying on the procedure of delivering nanoscale objects into targeted tumor tissues, which can release therapeutic killing doses of heat either upon AC magnetic field exposure or laser irradiation. Although an intense research effort has been made in recent years to study, separately, magnetic hyperthermia using iron oxide nanoparticles and photothermal therapy based on gold or silver plasmonic nanostructures, the full potential of combining both techniques has not yet been systematically explored. Here we present a proof-of-principle experiment showing that designing multifunctional silver/magnetite (Ag/Fe3O4) nanoflowers acting as dual hyperthermia agents is an efficient route for enhancing their heating ability or specific absorption rate (SAR). Interestingly, the SAR of the nanoflowers is increased by at least 1 order of magnitude under the application of both an external magnetic field of 200 Oe and simultaneous laser irradiation. Furthermore, our results show that the synergistic exploitation of the magnetic and photothermal properties of the nanoflowers reduces the magnetic field and laser intensities that would be required in the case that both external stimuli were applied separately. This constitutes a key step toward optimizing the hyperthermia therapy through a combined multifunctional magnetic and photothermal treatment and improving our understanding of the therapeutic process to specific applications that will entail coordinated efforts in physics, engineering, biology, and medicine.

In the present paper, a lab-made electromagnetic applicator for magnetic hyperthermia experiments is described, fabricated and tested. The proposed device is able to measure the specific absorption rate (SAR) of nanoparticle samples at different magnetic field intensities and frequencies. Based on a variable parallel LCC resonant circuit fed by a linear power amplifier, the electromagnetic applicator is optimized to generate a controllable and homogeneous AC magnetic field in a 3.5 cm3 cylindrical volume, in a wide frequency range of 149–1030 kHz with high field intensities (up to 35 kA m−1 at low frequencies and up to 22 kA m−1 at high frequencies). In addition, a lab-made AC magnetometer is integrated in the electromagnetic applicator. The AC magnetometer is fully compensated to provide accurate measurements of the dynamic hysteresis cycle for nanoparticle powders or dispersions. From these dynamic hysteresis loops the SAR of the nanoparticle samples can be directly obtained. To show the capabilities of the proposed set-up, the AC hysteresis loops of two different magnetite nanoparticle samples with different sizes have been measured for various field intensities and frequencies. To our knowledge, no other work reports an electromagnetic applicator system with integrated AC magnetometer providing such characteristics in terms of frequency and intensity.

We hereby present experimental and theoretical insights on the use of biomineralized magnetite nanoparticles, called magnetosomes, as heat nanoinductors in the magnetic hyperthermia technique. The heating efficiency or specific absorption rate of magnetosomes extracted from Magnetospirillum gryphiswaldense bacteria and immersed in water and agarose gel, was directly determined from the hysteresis loops obtained at different frequencies and magnetic field amplitudes. We demonstrate that heat production of magnetosomes can be predicted in the framework of the Stoner–Wohlfarth theory of uniaxial magnetic anisotropy subjected to significant dipolar interactions, which can be described in terms of an interaction anisotropy superimposed to that of each particle. Based on these findings, we propose optimal magnetic field amplitude and frequency values in order to maximize the heat production while keeping the undesired eddy current effects below safe and tolerable limits. The efficiency of magnetosomes as heat generators and their impact on cell viability has been checked in macrophage cells. Our results clearly indicate that the hyperthermia treatment causes both cell death and inhibition of cell proliferation. Specifically, only 36% of the treated macrophages remained alive 2 h after alternating magnetic field exposure, and 24 h later the percentage fell to 22%.