Magneto-Mechanical Nanoscale Actuation in Cancer Therapeutics: A Review
Yara Maayah, Sakura Rieck, Samuel Minier, Dhanushi Dedakia, Juan Beltran-HuaracAbstract
Magneto-mechanical actuation (MMA) is a potent tool in nanomedicine, particularly in cancer therapeutics. Recent studies have demonstrated the capabilities of MMA to induce significant cell death using magnetic nanoparticles (MNPs) remotely actuated by super-low frequency alternating magnetic fields (AMFs) without inducing detectable heat (nhMMA). The applications of MMA vary widely, including the physical disruption of cells to improve drug delivery and its use in conjunction with existing therapies (polytherapies) to amplify therapeutic outcomes. With so many different parameters, such as particle design (size and morphology), magnetic field dosage (frequency, amplitude, duration, and exposure mode), and cell type, that directly impact specific therapeutic outcomes, a summary of the main findings reported in the literature is imperative to understand the mechanism and origin of MMA. Nanoparticle design dictates their magnetic ordering and how they behave in biological settings, including an active role in cellular uptake, intracellular distribution, and physical interaction with organelles. Critically important is the magnetic response of MNPs in uniform AMFs and their corresponding mechanical torque, which can be tailored by physicochemical and magnetic parameters. In this sense, MNPs are artificially engineered to execute a specific action in single therapies and polytherapies, whether physical disruption of a subcellular target or the entire cell is required. Recent reports indicate that nhMMA can disrupt cell membranes, cytoskeletons, lysosomes, mitochondria, and membrane ion channels, thus triggering cell death through apoptosis or necrosis. This review aims to provide the relevant background, explain current and pragmatic considerations for study designs, and summarize study parameters, findings, and mechanisms that govern MMA. This review also accentuates the necessity for uniform magnetic exposures to generate reliable and reproducible data and reduce conflicting and contradicting inter-laboratory data reported in the literature. The therapeutic customization and remote control make MMA a tremendous tool to effectively pursue the treatment of cancer globally at any specialized level.