Vortex nano-discs: from micromagnetic simulations to cancer cells internalization for magneto-mechanically induced damage applications.

Abstract

The advances in synthesis methods and the research of new magnetic effects have been the driving forces propelling the use of magnetic nanostructures in several research fields. In biomedical applications, magnetic nanoparticles, usually in the superparamagnetic state, are mainly used in magnetic fluid hyperthermia (MFH) and as contrast agents. In contrast, the novel magnetic nanostructures (MNS) studied in this work present a unique spin arrangement in the magnetic ground state, namely spin-vortex or synthetic antiferromagnetic state. MNS are mainly produced using top-down lithography techniques and physical vapour deposition methods. They are not spherical, rather disc-shaped, like coins with nanometer dimensions. MNS showed promising results in cell separation, as a contrast enhancing agents in MRI and in magneto-mechanically induced cell annihilation. Magneto-mechanically induced cell annihilation is a comparable technique with MFH for cancer therapy, where instead of superparamagnetic particles, micro/nano-discs in the spin-vortex state or synthetic antiferromagnetic nanostructures are employed. The main advantages of this novel approach are the usage of weaker magnetic fields with lower frequencies, as well as the need for a lower concentration of particles. This scenario opens new possibilities in cancer therapy, having triggered a scientific interest for MNS with unique spin configurations suitable for biomedical applications [1].In this work, we developed one subset of biocompatible magnetic nanostructures that exhibit a spin-vortex state with interest in analysing their application in magneto-mechanically induced cell death [2]. First, micromagnetic simulations, using mumax3 of sub-micron iron discs, were performed for different interdot distance and aspect-ratio (thickness/diameter), to better understand the magnetic behaviour of these nanostructures. Two sets of samples were studied: ideal circular discs and disc-shaped nanostructures (based on images of real samples). By analysing the nucleation and annihilation fields, as well as the magnetic susceptibility, it was found that the (ideal) discs could be considered as isolated for interdot distances greater than twice the radius of the disc (2R) [3]. We also found that discs with an aspect ratio between 5 and 15 should sustain the vortex state in remanence.Iron nano-discs, with a diameter of about 500 nm, were fabricated by electron beam evaporation on a Si substrate pre-patterned by interference lithography [4]. The discs, protected by bottom and top gold layers, were fully characterized with scanning electron microscopy (SEM), X-ray diffraction (XRD), superconducting quantum interference device (SQUID), magneto-optic Kerr effect (MOKE) and ferromagnetic resonance (FMR) techniques. The synthesized nanostructures showed the desired vortex state configuration. The obtained magnetic measurements are in good agreement with the micromagnetic simulations (Fig. 1). Then, the magnetic vortex nano-discs were released from the substrate by chemical etching of a sacrificial layer. Subsequently, cell viability and uptake assays were performed in a human leukaemia monocyte cell line (THP-1). Several concentrations of nano-discs were studied by flow cytometry. As a result, the discs were internalized by the cells and found to be innocuous to them, in the absence of an external magnetic field.Work supported by Horizon 2020 MSCA grant agreement No 734801, AEI PID2019-104604RB, IT1162-19, IF/01159/2015, SFRH/BD/148563/2019, POCI-01-0145-FEDER-028676/PTDC/CTM-CTM/28676/2017 and POCI-01-0145-FEDER-031302/PTDC/FIS-MAC/31302/2017. **