We introduce a new type of magnetic particles (MPs) prepared by wet milling of superferromagnetic Fe-Cr-Nb-B precursor glassy ribbons for cancer treatment by magneto-mechanical actuation in low magnetic fields (1 ÷ 20 Oe). The rectangular shapes of MPs and the superferromagnetism of the glassy alloys of which are made the MPs induce important magnetic shape anisotropies which, in association with a large saturation magnetization, generate an improved torque in a rotating magnetic field, producing important damages on the cellular viability of MG-63 human osteosarcoma (HOS) cells. The specific parameters such as MPs concentration, frequency and intensity of the applied magnetic field, or the time of exposure have a strong influence on the cancer cells viability. The specific behavior of the Fe-Cr-Nb-B MPs offers them destructive effect even in low magnetic fields such as 10 Oe, and this characteristic allows the use of coils systems which provide large experimental spaces. The novel MPs are used for the magneto-mechanical actuation alone or in association with hyperthermia, but also can be transported to the tumor sites by means of stem cells carriers.

IntroductionHyperthermia (HT) based on magnetic nanoparticles (MNPs) represents a promising approach to induce the apoptosis/necrosis of tumor cells through the heat generated by MNPs submitted to alternating magnetic fields. However, the effects of temperature distribution on the cancer cells’ viability as well as heat resistance of various tumor cell types warrant further investigation.MethodsIn this work, the effects induced by magnetic hyperthermia (MHT) and conventional water-based hyperthermia (WHT) on the viability of human osteosarcoma cells at different temperatures (37°C–47°C) was comparatively investigated. Fe-Cr-Nb-B magnetic nanoparticles were submitted either to alternating magnetic fields or to infrared radiation generated by a water-heated incubator.ResultsIn terms of cell viability, significant differences could be observed after applying the two HT treatment methods. At about equal equilibrium temperatures, MHT was on average 16% more efficient in inducing cytotoxicity effects compared to WHT, as assessed by MTT cytotoxicity assay.ConclusionWe propose the phenomena can be explained by the significantly higher cytotoxic effects initiated during MHT treatment in the vicinity of the heat-generating MNPs compared to the effects triggered by the homogeneously distributed temperature during WHT. These in vitro results confirm other previous findings regarding the superior efficiency of MHT over WHT and explain the cytotoxicity differences observed between the two antitumor HT methods.

The use of materials at nanoscale is currently of increasing interest for life sciences and medicine. Magnetic nanoparticles (MNPs) are under scrutiny for a large array of applications in nanomedicine as diagnostic and therapeutic tools. Proprietary Fe-Cr-Nb-B MNPs display heating properties that recommends them as potent agents for delivery of local hyperthermia for the treatment of solid tumours. Stem cell mediated delivery represents a safe and accurate modality to target remote or metastatic tumour sites. In this study we investigated the interaction of Fe-Cr-Nb-B nanoparticles with human adipose derived mesenchymal stem cells and human primary osteoblasts. We found that: (a) bare and chitosan coated Fe-Cr-Nb-B are internalized by both cell types, (b) they can be detected up to 28 days inside the cells without signs of membrane disruption and (c) they do not display in vitro toxicity. MNPs are uploaded by cells in a time dependent manner with maximum uptake after 7-8 days cell-particle incubation. Particle internalization do not interfere with proliferative and differentiation potential (osteogenesis and adipogenesis) demonstrating an unaltered cellular phenotype. Further investigation of the potential effect of MNPs internalization on cytoskeleton dynamics and in inducing oxidative stress will be required as it is of interest for predicting cell migration and survival after transplantation. Present results are encouraging for designing a stemcell mediated delivery of Fe-Cr-Nb-B magnetic nanoparticles to solid tumour sites for hyperthermia applications.

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A ferrofluid based on Fe67.2Cr12.5Nb0.3B20 magnetic particles with a low Curie temperature was prepared. The particles, most of which had dimensions under 60 nm, were dispersed in a calcium gluconate solution, leading to a stable ferrofluid. The obtained ferrofluid had a magnetization of 0.04 to 0.17 emu/cm3, depending on the particles’ concentration, and a viscosity that increased nonlinearly with the applied magnetic field. The ferrofluid appeared to be biocompatible, as it showed low cytotoxicity, even at high concentrations and for long intervals of co-incubation with human cells, demonstrating a good potential to be used for cancer therapies through magnetic hyperthermia as well as magneto-mechanical actuation.