Magnetic Nanodiscs-A New Promising Tool for Microsurgery of Malignant Neoplasms

Abstract

Magnetomechanical therapy is one of the most perspective directions in tumor microsurgery. According to the analysis of recent publications, it can be concluded that a nanoscalpel could become an instrument sufficient for cancer microsurgery. It should possess the following properties: (1) nano- or microsized; (2) affinity and specificity to the targets on tumor cells; (3) remote control. This nano- or microscalpel should include at least two components: (1) a physical nanostructure (particle, disc, plates) with the ability to transform the magnetic moment to mechanical torque; (2) a ligand-a molecule (antibody, aptamer, etc.) allowing the scalpel precisely target tumor cells. Literature analysis revealed that the most suitable nanoscalpel structures are anisotropic, magnetic micro- or nanodiscs with high-saturation magnetization and the absence of remanence, facilitating scalpel remote control via the magnetic field. Additionally, anisotropy enhances the transmigration of the discs to the tumor. To date, four types of magnetic microdiscs have been used for tumor destruction: synthetic antiferromagnetic P-SAF (perpendicular) and SAF (in-plane), vortex Py, and three-layer non-magnetic-ferromagnet-non-magnetic systems with flat quasi-dipole magnetic structures. In the current review, we discuss the biological effects of magnetic discs, the mechanisms of action, and the toxicity in alternating or rotating magnetic fields in vitro and in vivo. Based on the experimental data presented in the literature, we conclude that the targeted and remotely controlled magnetic field nanoscalpel is an effective and safe instrument for cancer therapy or theranostics.

Keywords: magnetic field; magnetomechanical therapy; microdiscs; nanodiscs; the nanoscalpel.

Figure 1

Schematic representation of the novel nanoscalpel device (a): binding selectively to tumor cells (b) for different applications (c) such as accurate diagnostics and targeted therapy (d).

Figure 2

Magnetic discs are used to destroy tumor cells: synthetic antiferromagnetic P-SAF and SAF, vortex Py, and three-layer non-magnetic–ferromagnetic–non-magnetic systems with a flat quasi-dipole magnetic structure. P-SAF: Out-of-plane magnetic moments. Zero remanences. Under a magnetic field, the disc is magnetized with out-of-plane net magnetization. SAF: In-plane magnetic moments. Zero remanences. Under a magnetic field, the disc is magnetized with in-plane net magnetization. Vortex Py: In-plane magnetic moments. Zero remanences. Under a magnetic field, the disc is magnetized with in-plane net magnetization. Discs with a flat quasi-dipole magnetic structure: In-plane magnetic moments. Zero remanences. Under a magnetic field, the disc is magnetized with in-plane net magnetization.

Figure 3

The biological effects of magnetic nano- or microdiscs functionalized by recognizing molecules, which in the low-frequency magnetic field act inside the cell after internalization by endocytosis (a) or directly influence the cellular membrane by interacting with membrane proteins (b), causing apoptosis (c) or necrosis (d).

Figure 4

Schematic diagram showing changes of the target cell’s functional state under the influence of magnetic discs and the effects on membrane proteins in an alternating or rotating magnetic field. In a magnetic field, the discs’ forces act on the cell membrane and cytoskeleton in two ways: directly (a) or indirectly through the target protein (b).

Figure 5

Tumor vasculature (a) in a complex tumor microenvironment (transformed and immune cells) (b). Transport of magnetic anisotropic discs and spherical magnetic nanoparticles along transformed tumor vessels (c). Spherical particles move in the central part of the vascular bed, while anisotropic magnetic discs move along the periphery of the vessel, frequently interacting with the vessel wall; this peculiarity facilitates discs transmigration into the tumor (c). Magnetic nanodiscs are able to pass into a tumor through the damaged basal membrane in two ways: through endothelial cells and the gaps between them (d).