D. Ortega

Fundamentals and advances in magnetic hyperthermia

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.

Superparamagnetic iron oxide nanoparticle targeting of MSCs in vascular injury

Vascular occlusion can result in fatal myocardial infarction, stroke or loss of limb in peripheral arterial disease. Interventional balloon angioplasty is a common first line procedure for vascular disease treatment, but long term success is limited by restenosis and neointimal hyperplasia. Cellular therapies have been proposed to mitigate these issues; however efficacy is low, in part due to poor cell retention. We show that magnetic targeting of mesenchymal stem cells gives rise to a 6-fold increase in cell retention following balloon angioplasty in a rabbit model using a clinically applicable permanent magnet. Cells labelled with superparamagnetic iron oxide nanoparticles exhibit no negative effects on cell viability, differentiation or secretion patterns. The increase in stem cell retention leads to a reduction in restenosis three weeks after cell delivery.

Engineering Iron Oxide Nanoparticles for Clinical Settings

Iron oxide nanoparticles (IONPs) occupy a privileged position among magnetic nanomaterials with potential applications in medicine and biology. They have been widely used in preclinical experiments for imaging contrast enhancement, magnetic resonance, immunoassays, cell tracking, tissue repair, magnetic hyperthermia and drug delivery. Despite these promising results, their successful translation into a clinical setting is strongly dependent upon their physicochemical properties, toxicity and functionalization possibilities. Currently, IONPs-based medical applications are limited to the use of non-functionalized IONPs smaller than 100 nm, with overall narrow particle size distribution, so that the particles have uniform physical and chemical properties. However, the main entry of IONPs into the scene of medical application will surely arise from their functionalization possibilities that will provide them with the capacity to target specific cells within the body, and hence to play a role in the development of specific therapies. In this review, we offer an overview of their basic physicochemical design parameters, giving an account of the progress made in their functionalization and current clinical applications. We place special emphasis on past and present clinical trials.

Real-time tracking of delayed-onset cellular apoptosis induced by intracellular magnetic hyperthermia

AIM To assess cell death pathways in response to magnetic hyperthermia. MATERIALS & METHODS Human melanoma cells were loaded with citric acid-coated iron-oxide nanoparticles, and subjected to a time-varying magnetic field. Pathways were monitored in vitro in suspensions and in situ in monolayers using fluorophores to report on early-stage apoptosis and late-stage apoptosis and/or necrosis. RESULTS Delayed-onset effects were observed, with a rate and extent proportional to the thermal-load-per-cell. At moderate loads, membranal internal-to-external lipid exchange preceded rupture and death by a few hours (the timeline varying cell-to-cell), without any measurable change in the local environment temperature. CONCLUSION Our observations support the proposition that intracellular heating may be a viable, controllable and nonaggressive in vivo treatment for human pathological conditions.

Room temperature spontaneous magnetization in calcined trioctylphosphine-ZnO nanoparticles

In this work, it is demonstrated that capping with trioctylphosphine oxide (TOPO) induces a ferromagnetic response in free-standing ZnO nanoparticles upon calcination without the necessity of metallic doping. Samples were synthesized by precipitation of zinc acetate solutions in a basic medium followed by capping with TOPO and heat treatment in static aerobic conditions. Nanoparticles show a wurtzite-type structure with an average size of 14 nm, and magnetization measurements evidence a spontaneous magnetic moment at room temperature for calcined nanoparticles, in contrast with the diamagnetic response observed in non-calcined TOPO-capped nanoparticles. Giving the absence of any magnetic impurity or metal dopant that could account for the total magnetization, it is proposed that the magnetism would be consistent with a charge transfer mechanism promoted by a phosphorous doping upon calcination of TOPO over the nanoparticles. This situation leads to a spontaneous magnetic moment by the local fulfillment of Stoner’s criterion for ferromagnetism at the nanoparticles surface.

Elucidating the morphological and structural evolution of iron oxide nanoparticles formed by sodium carbonate in aqueous medium

Ferrimagnetic iron oxides are the common choice for many current technologies, especially those with application in biology and medicine. Despite the comprehensive knowledge accumulated about their chemistry in the bulk state, the sequence of changes taking place during the precipitation of iron oxide nanoparticles in aqueous media is much less extensive. We show that using sodium carbonate as a co-precipitating agent for the synthesis of uncoated iron oxide nanoparticles, the reaction proceeds sufficiently slowly to enable a detailed study of both the reaction pathway and products. The effect of pH, temperature and reaction time on particle size, morphology, crystalline phase and its magnetic properties was investigated. The obtained nanoparticles showed an increase in average particle size of about 10 nm per pH unit for the magnetite phase leading to 6.9 ± 0.4 nm, 18 ± 3 nm and 28 ± 5 nm for pH 8, 9 and 10 respectively. Goethite was initially formed by an olation mechanism at room temperature, followed by a slow transformation into magnetite over a 24 h period, as tracked by X-ray diffraction. In another set of experiments where the reaction temperatures were varied, magnetite was obtained directly by the oxolation mechanism at temperatures above 45 °C. The optimization of the experimental parameters led to superparamagnetic nanoparticles with a high saturation magnetization of 82 A m2 kg−1 at 300 K when synthesized at pH 9.

Size and surface effects in the magnetic properties of maghemite and magnetite coated nanoparticles

An increasing number of promising applications for future technology is arising from size constraints in nanoparticles (NPs) and from the chemical manipulation of their surfaces. In this work, we analyse the finite-size and surface effects on polyacrylic acid-coated Fe3O4 NPs and oleic acid-coated γ-Fe2O3 NPs by studying their magnetization curves at different temperatures. The measured thermal dependence of the saturation magnetization is no longer explained by the typical T3/2 Bloch law, yielding higher values than those expected for its exponent. When incorporated in polymeric matrixes to form magnetic transparent nanocomposites, the oleic acid-coated γ-Fe2O3 NPs also deviate from Bloch’s law, but following the opposite trend observed in free coated NPs.

Electric field-assisted levitation-jet aerosol synthesis of Ni/NiO nanoparticles

Ni/NiO powdered nanoparticles with average sizes 10–30 nm were prepared by a levitation-jet method involving the condensation of Ni metal vapour in a mixture of helium with various amounts of air or oxygen. The process was undertaken with the application of a DC electric field up to 6.5 kV cm−1. The particles were characterized by X-Ray diffraction, transmission electron microscopy, BET adsorption and vibrating sample magnetometry. It was found that the intensity of the applied electric field and partial oxygen pressure correlated with the main structural and magnetic parameters of the nanoparticles, such as average particle size, residual ratio of nickel, coercivity and maximum magnetisation. The specific surface area of the particles correlated with the magnitude of the external electric field. Room-temperature hysteresis loops of weakly oxidized nanoparticles show ferromagnetic-like behaviour, whereas the strongly oxidized ones exhibit a low-field ferromagnetic feature superimposed to a paramagnetic signal, regardless of the particle size. Magnetic measurements allowed for the estimation of the residual metal Ni content in the powdered nanoparticles, which can be as low as 0.04 at.% depending on oxygen partial pressure and external electric field strength.

Nonylphenol polyethoxylate coated body-center-cubic iron nanocrystals for ferrofluids with technical applications

An approach to the design of a suitable system for technological applications, such as magneto-rheological fluids with controllable performance, showing high saturation magnetization and low coercivity and remanence, is presented. This approach is based on the synthesis of stable iron nanoparticles with a relatively thick polymeric coating—the non-ionic surfactant nonylphenol polyethoxylate—by a microemulsion method with NaBH4 as a reducing agent. X-ray diffractometry, Mossbauer spectroscopy, and high resolution electron microscopy reveal a body-center-cubic structure in the iron cores. The resulting nanoparticles are predominantly spherical, having an average core size of 7 nm and a constant shell thickness of 3 nm. Magnetic measurements reveal a higher saturation magnetization (127.4 Am2 kg−1 at 300 K and 153.2 Am2 kg−1 at 5 K) than in other approaches and a small coercive field of 12 mT. X-ray diffractometry results account for the presence of iron borate traces as a secondary phase, formed at the init...

Rapid magnetic cell delivery for large tubular bioengineered constructs

Delivery of cells into tubular tissue constructs with large diameters poses significant spatial and temporal challenges. This study describes preliminary findings for a novel process for rapid and uniform seeding of cells onto the luminal surface of large tubular constructs. Fibroblasts, tagged with superparamagnetic iron oxide nanoparticles (SPION), were directed onto the luminal surface of tubular constructs by a magnetic field generated by a k4-type Halbach cylinder device. The spatial distribution of attached cells, as measured by the mean number of cells, was compared with a conventional, dynamic, rotational cell-delivery technique. Cell loading onto the constructs was measured by microscopy and magnetic resonance imaging. The different seeding techniques employed had a significant effect on the spatial distribution of the cells (p < 0.0001). The number of attached cells at defined positions within the same construct was significantly different for the dynamic rotation technique (p < 0.05). In contrast, no significant differences in the number of cells attached to the luminal surface were found between the defined positions on the construct loaded with the Halbach cylinder. The technique described overcomes limitations associated with existing cell-delivery techniques and is amenable to a variety of tubular organs where rapid loading and uniform distribution of cells for therapeutic applications are required.