Synthesis and properties of nickel-cobalt-boron nanoparticles

morphous cobalt nickel boride nanoparticles were synthesised by chemical reduction synthesis in aqueous solution. Careful control of synthesis conditions and post reaction oxidation enabled the nanoparticles to be converted into a core-shell structure comprising of an amorphous Co–Ni–B core and an outer metal oxide sheet. These particles had interesting magnetic properties including saturation magnetisations and coercivities of the order of 80 emu/g and 170 Oe respectively, making them suitable for a potential use as an exchange-pinned magnetic material

Superparamagnetic particles in ZSM-5-type ferrisilicates

As-synthesized, low iron content, ferrisilicates of ZSM-5-type contain well-separated Fe(III) ions in a tetrahedral environment and display paramagnetic behavior. After hydrothermal treatment, the iron ions are partially extracted from the framework, generating nanosize iron oxide or oxyhydroxide ferrimagnetic particles. This process has been studied by transmission electron microscopy (TEM), Mossbauer spectroscopy, magnetic ac susceptibility (chi(ac)), and field dependent magnetization, on samples containing up to 6.7 wt. % Fe. The experiments evidence the growth of nonaggregated particles, with a typical size around 3 nm, presumably located at the surface of the ferrisilicate crystallites, From a thorough granulometric analysis involving TEM and chi(ac) data, it is concluded that, in the range from 1.5 to 4.6 wt. % Fe, the particle size distributions are significantly independent of the iron content

Superparamagnetic iron oxide nanoparticles regulate smooth muscle cell phenotype

Superparamagnetic iron oxide nanoparticles are used for an increasing range of biomedical applications, from imaging to mechanical actuation of cells and tissue. The aim of this study was to investigate the loading of smooth muscle cells with superparamagnetic iron oxide nanoparticles and to explore what effect this has on the phenotype of the cells. Adherent human smooth muscle cells were loaded with ∼17 pg of unconjugated, negatively charged, 50 nm superparamagnetic iron oxide nanoparticles (SPION). Clusters of the internalized SPION particles were held in discrete cytoplasmic vesicles. Internalized SPION did not cause any change in cell morphology, proliferation, metabolic activity, or staining pattern of actin and calponin, two of the muscle contractile proteins involved in force generation. However, internalized SPION inhibited the increased gene expression of actin and calponin normally observed when cells are incubated under differentiation conditions. The observed change in the control of gene expression of muscle contractile apparatus by SPION has not previously been described. This finding could offer novel approaches for regulating the phenotype of smooth muscle cells and warrants further investigation. This article is protected by copyright. All rights reserved

Hyperthermia treatment of tumors by mesenchymal stem cell-delivered superparamagnetic iron oxide nanoparticles.

Magnetic hyperthermia - a potential cancer treatment in which superparamagnetic iron oxide nanoparticles (SPIONs) are made to resonantly respond to an alternating magnetic field (AMF) and thereby produce heat - is of significant current interest. We have previously shown that mesenchymal stem cells (MSCs) can be labeled with SPIONs with no effect on cell proliferation or survival and that within an hour of systemic administration, they migrate to and integrate into tumors in vivo. Here, we report on some longer term (up to 3 weeks) post-integration characteristics of magnetically labeled human MSCs in an immunocompromized mouse model. We initially assessed how the size and coating of SPIONs dictated the loading capacity and cellular heating of MSCs. Ferucarbotran(®) was the best of those tested, having the best like-for-like heating capability and being the only one to retain that capability after cell internalization. A mouse model was created by subcutaneous flank injection of a combination of 0.5 million Ferucarbotran-loaded MSCs and 1.0 million OVCAR-3 ovarian tumor cells. After 2 weeks, the tumors reached ~100 µL in volume and then entered a rapid growth phase over the third week to reach ~300 µL. In the control mice that received no AMF treatment, magnetic resonance imaging (MRI) data showed that the labeled MSCs were both incorporated into and retained within the tumors over the entire 3-week period. In the AMF-treated mice, heat increases of ~4°C were observed during the first application, after which MRI indicated a loss of negative contrast, suggesting that the MSCs had died and been cleared from the tumor. This post-AMF removal of cells was confirmed by histological examination and also by a reduced level of subsequent magnetic heating effect. Despite this evidence for an AMF-elicited response in the SPION-loaded MSCs, and in contrast to previous reports on tumor remission in immunocompetent mouse models, in this case, no significant differences were measured regarding the overall tumor size or growth characteristics. We discuss the implications of these results on the clinical delivery of hyperthermia therapy to tumors and on the possibility that a preferred therapeutic route may involve AMF as an adjuvant to an autologous immune response

Anisotropy field measurement in barium ferrite powders by applied field MSssbauer spectroscopy

A new method for measuring magnetic anisotropy in ferrimagnetic powders using applied field Mossbauer spectroscopy has been developed. The method is based on using a uniaxial anisotropy mean-field model to calculate the equilibrium spin orientations as a function of applied field and compute the corresponding Mossbauer spectra. A variety of asymmetric broad line profiles are predicted which are sensitively dependent on the magnetization and the exchange and anisotropy terms. In principle the technique enables the determination of individual sublattice anisotropies, although in the case of pure and Co-Ti substituted barium ferrite the sublattice anisotropies are found to be experimentally indistinguishable. A mean anisotropy is obtained which compares favourably with the results of other measurements on barium ferrite

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

Hyperthermia treatment of tumors by mesenchymal stem cell-delivered superparamagnetic iron oxide nanoparticles

Magnetic hyperthermia – a potential cancer treatment in which superparamagnetic iron oxide nanoparticles (SPIONs) are made to resonantly respond to an alternating magnetic field (AMF) and thereby produce heat – is of significant current interest. We have previously shown that mesenchymal stem cells (MSCs) can be labeled with SPIONs with no effect on cell proliferation or survival and that within an hour of systemic administration, they migrate to and integrate into tumors in vivo. Here, we report on some longer term (up to 3 weeks) post-integration characteristics of magnetically labeled human MSCs in an immunocompromized mouse model. We initially assessed how the size and coating of SPIONs dictated the loading capacity and cellular heating of MSCs. Ferucarbotran® was the best of those tested, having the best like-for-like heating capability and being the only one to retain that capability after cell internalization. A mouse model was created by subcutaneous flank injection of a combination of 0.5 million Ferucarbotran-loaded MSCs and 1.0 million OVCAR-3 ovarian tumor cells. After 2 weeks, the tumors reached ~100 µL in volume and then entered a rapid growth phase over the third week to reach ~300 µL. In the control mice that received no AMF treatment, magnetic resonance imaging (MRI) data showed that the labeled MSCs were both incorporated into and retained within the tumors over the entire 3-week period. In the AMF-treated mice, heat increases of ~4°C were observed during the first application, after which MRI indicated a loss of negative contrast, suggesting that the MSCs had died and been cleared from the tumor. This post-AMF removal of cells was confirmed by histological examination and also by a reduced level of subsequent magnetic heating effect. Despite this evidence for an AMF-elicited response in the SPION-loaded MSCs, and in contrast to previous reports on tumor remission in immunocompetent mouse models, in this case, no significant differences were measured regarding the overall tumor size or growth characteristics. We discuss the implications of these results on the clinical delivery of hyperthermia therapy to tumors and on the possibility that a preferred therapeutic route may involve AMF as an adjuvant to an autologous immune response

On the 'centre of gravity' method for measuring the composition of magnetite/maghemite mixtures, or the stoichiometry of magnetite-maghemite solid solutions, via Fe-57 Mossbauer spectroscopy

We evaluate the application of 57Fe Mössbauer spectroscopy to the determination of the composition of magnetite (Fe3O4)/maghemite (γ-Fe2O3) mixtures and the stoichiometry of magnetite-maghemite solid solutions. In particular, we consider a recently proposed model-independent method which does not rely on a priori assumptions regarding the nature of the sample, other than that it is free of other Fe-containing phases. In it a single parameter, δRT—the ‘centre of gravity’, or area weighted mean isomer shift at room temperature, T = 295 ± 5 K—is extracted by curve-fitting a sample’s Mössbauer spectrum, and is correlated to the sample’s composition or stoichiometry. We present data on highpurity magnetite and maghemite powders, and mixtures thereof, as well as comparison literature data from nanoparticulate mixtures and solid solutions, to show that a linear correlation exists between δRT and the numerical proportion of Fe atoms in the magnetite environment: α = Femagnetite/Fetotal = − ( ) δ δ RT o /m, where δo = 0.3206 ± 0.0022mm s−1 and m = 0.2135 ± 0.0076mm s−1 . We also present equations to relate α to the weight percentage w of magnetite in mixed phases, and the magnetite stoichiometry x = Fe2+/Fe3+ in solid solutions. The analytical method is generally applicable, but is most accurate when the absorption profiles are sharp; in some samples this may require spectra to be recorded at reduced temperatures. We consider such cases and provide equations to relate δ ( ) T to the corresponding α value

Magnetic Oculomotor Prosthetics for Acquired Nystagmus

PURPOSE: Acquired nystagmus, a highly symptomatic consequence of damage to the substrates of oculomotor control, often is resistant to pharmacotherapy. Although heterogeneous in its neural cause, its expression is unified at the effector-the eye muscles themselves-where physical damping of the oscillation offers an alternative approach. Because direct surgical fixation would immobilize the globe, action at a distance is required to damp the oscillation at the point of fixation, allowing unhindered gaze shifts at other times. Implementing this idea magnetically, herein we describe the successful implantation of a novel magnetic oculomotor prosthesis in a patient. DESIGN: Case report of a pilot, experimental intervention. PARTICIPANT: A 49-year-old man with longstanding, medication-resistant, upbeat nystagmus resulting from a paraneoplastic syndrome caused by stage 2A, grade I, nodular sclerosing Hodgkin's lymphoma. METHODS: We designed a 2-part, titanium-encased, rare-earth magnet oculomotor prosthesis, powered to damp nystagmus without interfering with the larger forces involved in saccades. Its damping effects were confirmed when applied externally. We proceeded to implant the device in the patient, comparing visual functions and high-resolution oculography before and after implantation and monitoring the patient for more than 4 years after surgery. MAIN OUTCOME MEASURES: We recorded Snellen visual acuity before and after intervention, as well as the amplitude, drift velocity, frequency, and intensity of the nystagmus in each eye. RESULTS: The patient reported a clinically significant improvement of 1 line of Snellen acuity (from 6/9 bilaterally to 6/6 on the left and 6/5-2 on the right), reflecting an objectively measured reduction in the amplitude, drift velocity, frequency, and intensity of the nystagmus. These improvements were maintained throughout a follow-up of 4 years and enabled him to return to paid employment. CONCLUSIONS: This work opens a new field of implantable therapeutic devices-oculomotor prosthetics-designed to modify eye movements dynamically by physical means in cases where a purely neural approach is ineffective. Applied to acquired nystagmus refractory to all other interventions, it is shown successfully to damp pathologic eye oscillations while allowing normal saccadic shifts of gaze

Commentary on the clinical and preclinical dosage limits of interstitially administered magnetic fluids for therapeutic hyperthermia based on current practice and efficacy models

We offer a critique of what constitutes a suitable dosage limit, in both clinical and preclinical studies, for interstitially administered magnetic nanoparticles in order to enable therapeutic hyperthermia under the action of an externally applied alternating magnetic field. We approach this first from the perspective of the currently approved clinical dosages of magnetic nanoparticles in the fields of MRI contrast enhancement, sentinel node detection, iron replacement therapy and magnetic thermoablation. We compare this to a simple analytical model of the achievable hyperthermia temperature rise in both humans and animals based on the interstitially administered dose, the heating and dispersion characteristics of the injected fluid, and the strength and frequency of the applied magnetic field. We show that under appropriately chosen conditions a therapeutic temperature rise is achievable in clinically relevant situations. We also show that in such cases it may paradoxically be harder to achieve the same therapeutic temperature rise in a preclinical model. We comment on the implications for the evidence-based translation of hyperthermia based interventions from the laboratory to the clinic