Magneto-mechanical destruction of cancer-associated fibroblasts using ultra-small iron oxide nanoparticles and low frequency rotating magnetic fields.

The destruction of cells using the mechanical activation of magnetic nanoparticles with low-frequency magnetic fields constitutes a recent and interesting approach in cancer therapy. Here, we showed that superparamagnetic iron oxide nanoparticles as small as 6 nm were able to induce the death of pancreatic cancer-associated fibroblasts, chosen as a model. An exhaustive screening of the amplitude, frequency, and type (alternating vs. rotating) of magnetic field demonstrated that the best efficacy was obtained for a rotating low-amplitude low-frequency magnetic field (1 Hz and 40 mT), reaching a 34% ratio in cell death induction; interestingly, the cell death was not maximized for the largest amplitudes of the magnetic field. State-of-the-art kinetic Monte-Carlo simulations able to calculate the torque undergone by assemblies of magnetic nanoparticles explained these features and were in agreement with cell death experiments. Simulations showed that the force generated by the nanoparticles once internalized inside the lysosome was around 3 pN, which is in principle not large enough to induce direct membrane disruption. Other biological mechanisms were explored to explain cell death: the mechanical activation of magnetic nanoparticles induced lysosome membrane permeabilization and the release of the lysosome content and cell death was mediated through a lysosomal pathway depending on cathepsin-B activity. Finally, we showed that repeated rotating magnetic field exposure halted drastically the cell proliferation. This study established a proof-of-concept that ultra-small nanoparticles can disrupt the tumor microenvironment through mechanical forces generated by mechanical activation of magnetic nanoparticles upon low-frequency rotating magnetic field exposure, opening new opportunities for cancer therapy.

Real-Time Observation and Analysis of Magnetomechanical Actuation of Magnetic Nanoparticles in Cells.

The origin of cell death in the magnetomechanical actuation of cells induced by magnetic nanoparticle motion under low-frequency magnetic fields is still elusive. Here, a miniaturized electromagnet fitted under a confocal microscope is used to observe in real time cells specifically targeted by superparamagnetic nanoparticles and exposed to a low-frequency rotating magnetic field. Our analysis reveals that the lysosome membrane is permeabilized in only a few minutes after the start of magnetic field application, concomitant with lysosome movements toward the nucleus. Those events are associated with disorganization of the tubulin microtubule network and a change in cell morphology. This miniaturized electromagnet will allow a deeper insight into the physical, molecular, and biological process occurring during the magnetomechanical actuation of magnetic nanoparticles.

Epitaxial growth of TbFe2 on piezoelectric LiNbO3 Z-cut.

The strongly magnetostrictive TbFe2 compound has been epitaxially grown on Z-cut Lithium Niobate (LiNbO3) substrates after the deposition of various buffer layers (Mo, Ti and Ti/Mo). Detailed and combined RHEED and x-ray analysis permitted to unravel the in-plane and relative orientation relationships (OR) of the different materials in the system. Despite the use of different templates with different structural orders, similar final OR are eventually found between the piezoelectric substrate and the magnetic layer. The structural and magnetic properties are analyzed in order to get a TbFe2 layer of optimum quality to build a magnetostrictive/piezoelectric hybrid system with efficient strain mediated coupling. Such systems are of interest for the development of magnetic sensors as well as for the electric control of magnetization.

Epitaxial growth of magnetostrictive TbFe2 films on piezoelectric LiNbO3.

The TbFe2 compound has been deposited by molecular beam epitaxy on lithium niobate (LN) substrates with different orientations (LN Z-, 128 Y- and 41 Y-cuts). Despite the challenging growth on these unconventional substrates, crystalline TbFe2 films (as a single orientated domain or with a limited number of orientations) of reasonable structural quality could be obtained after the deposition of a Mo buffer layer. Detailed and combined RHEED and x-ray analysis permitted to unravel the complex Mo and TbFe2 crystal orientations and to reveal common 3D orientation relationships between the different lattices, whatever the initial LN cut. The magnetic properties and especially the magnetic anisotropy have been investigated in taking magnetocrystalline, magnetoelastic and magnetostatic contributions into account. These promising results on the epitaxial growth of hybrid piezoelectric/magnetostrictive crystalline system constitute an important step towards the control of magnetization via electrically generated static and/or dynamic strains, and towards the development of magnetic sensors based on surface acoustic wave devices.

Cubic chemically ordered FeRh and FeCo nanomagnets prepared by mass-selected low-energy cluster-beam deposition: a comparative study.

Near the point of equiatomic composition, both FeRh and FeCo bulk alloys exhibit a CsCl-type (B2) chemically ordered phase that is related to specific magnetic properties, namely a metamagnetic anti-ferromagnetic/ferromagnetic transition near room temperature for FeRh and a huge magnetic moment for the FeCo soft alloy. In this paper, we present the magnetic and structural properties of nanoparticles of less than 5 nm diameter embedded in an inert carbon matrix prepared by mass-selected low-energy cluster-beam deposition technique. We obtained a CsCl-type (B2) chemically ordered phase for annealed nanoalloys. Using different experimental measurements, we show how decreasing the size affects the magnetic properties. FeRh nanoparticles keep the ferromagnetic order at low temperature due to surface relaxation affecting the cell parameter. In the case of FeCo clusters, the environment drastically affects the intrinsic properties of this system by reducing the magnetization in comparison to the bulk.

Nontrivial redox behavior of nanosized cobalt: new insights from ambient pressure X-ray photoelectron and absorption spectroscopies.

The reduction and oxidation of carbon-supported cobalt nanoparticles (3.50±0.22 nm) and a Co (0001) single crystal was investigated by ambient pressure X-ray photoelectron (APPES) and X-ray absorption (XAS) spectroscopies, applied in situ under 0.2 mbar hydrogen or oxygen atmospheres and at temperatures up to 620 K. It was found that cobalt nanoparticles are readily oxidized to a distinct CoO phase, which is significantly more stable to further oxidation or reduction compared to the thick oxide films formed on the Co(0001) crystal. The nontrivial size-dependence of redox behavior is followed by a difference in the electronic structure as suggested by theoretical simulations of the Co L-edge absorption spectra. In particular, contrary to the stable rocksalt and spinel phases that exist in the bulk oxides, cobalt nanoparticles contain a significant portion of metastable wurtzite-type CoO.