Remote manipulation of magnetic nanoparticles using magnetic field gradient to promote cancer cell death

Abstract

The manipulation of magnetic nanoparticles (MNPs) using an external magnetic field, has been demonstrated to be useful in various biomedical applications. Some techniques have evolved utilizing this non-invasive external stimulus but the scientific community widely adopts few, and there is an excellent potential for more novel methods. The primary focus of this study is on understanding the manipulation of MNPs by a time-varying static magnetic field and how this can be used, at different frequencies and displacement, to manipulate cellular function.Here we explore, using numerical modeling, the physical mechanism which underlies this kind of manipulation, and we discuss potential improvements which would enhance such manipulation with its use in biomedical applications, i.e., increasing the MNP response by improving the field parameters. From our observations and other related studies, we infer that such manipulation depends mostly on the magnetic field gradient, the magnetic susceptibility and size of the MNPs, the magnet array oscillating frequency, the viscosity of the medium surrounding MNPs, and the distance between the magnetic field source and the MNPs. Additionally, we demonstrate cytotoxicity in neuroblastoma (SH-SY5Y) and hepatocellular carcinoma (HepG2) cells in vitro. This was induced by incubation with MNPs, followed by exposure to a magnetic field gradient, physically oscillating at various frequencies and displacement amplitudes. Even though this technique reliably produces MNP endocytosis and/or cytotoxicity, a better biophysical understanding is required to develop the mechanism used for this precision manipulation of MNPs, in vitro.

Enhanced In Vitro Magnetic Cell Targeting of Doxorubicin-Loaded Magnetic Liposomes for Localized Cancer Therapy

“…The model remarkably predicted the experimental results, showing how internalization mostly occurred in correspondence of the magnet boundary (besides some layers close to the channel side boundary, where capture was favored by slow speed, i.e., viscous effects). This is in consistent with the fact that magnetic attraction is more pronounced close to the edge of the permanent magnet due to well-known field and gradient effects [ 57 , 58 , 59 ]. Overall, the possibility to accurately model the considered dynamic targeting strategy fosters the quantitative characterization and design of related approaches, in turn supporting potential translation to more clinically-relevant frameworks in the longer term.…”

Tailoring Iron Oxide Nanoparticles for Efficient Cellular Internalization and Endosomal Escape

“…Similar results have been observed by other research groups [ 381 , 382 ]. In contrast, other publications have shown that as opposed to static magnetic fields, the oscillatory ones facilitate uptake and led to superior MF [ 380 , 383 , 384 , 385 ]. However, the evidence is not compelling enough to elucidate whether this is also the case for endosomal escape.…”