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.

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.

This study provides a guide to maximizing hysteretic loss by matching the design and synthesis of superparamagnetic nanoparticles to the desired hyperthermia application. The maximal heat release from magnetic nanoparticles to the environment depends on intrinsic properties of magnetic nanoparticles (e.g. size, magnetization, and magnetic anisotropy), and extrinsic properties of the applied fields (e.g. frequency, field strength). Often, the biomedical hyperthermia application limits flexibility in setting of many parameters (e.g. nanoparticle size and mobility, field strength and frequency). We show that core-shell nanoparticles combining a soft (Mn ferrite) and a hard (Co ferrite) magnetic material form a system in which the effective magnetic anisotropy can be easily tuned independently of the nanoparticle size. A theoretical framework to include the crystal anisotropy contribution of the Co ferrite phase to the nanoparticles total anisotropy is developed. The experimental results confirm that this framework predicts the hysteretic heating loss correctly when including non-linear effects in an effective susceptibility. Hence, we provide a guide on how to characterize the magnetic anisotropy of core-shell magnetic nanoparticles, model the expected heat loss and therefore, synthesize tuned nanoparticles for a particular biomedical application.

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%.

Magnetospirillum gryphiswaldense is a microorganism with the ability to biomineralize magnetite nanoparticles, called magnetosomes, and arrange them into a chain that behaves like a magnetic compass. Rather than straight lines, magnetosome chains are slightly bent, as evidenced by electron cryotomography. Our experimental and theoretical results suggest that due to the competition between the magnetocrystalline and shape anisotropies, the effective magnetic moment of individual magnetosomes is tilted out of the [111] crystallographic easy axis of magnetite. This tilt does not affect the direction of the chain net magnetic moment, which remains along the [111] axis, but explains the arrangement of magnetosomes in helical-like shaped chains. Indeed, we demonstrate that the chain shape can be reproduced by considering an interplay between the magnetic dipolar interactions between magnetosomes, ruled by the orientation of the magnetosome magnetic moment, and a lipid/protein-based mechanism, modeled as an elastic recovery force exerted on the magnetosomes.