Magneto-mechanical therapeutic effects and associated cell death pathways of magnetic nanocomposites with distinct geometries.

Recent years have witnessed important developments in the emerging field of magneto-mechanical therapies. While such approaches have been demonstrated as a highly efficient route to augment, complement, or entirely replace other therapeutic strategies, important aspects are still poorly understood. Among these, the dependence between the cell death pathway and the geometry of magnetic nanocomposites enabling magneto-mechanical therapies under a low-frequency rotating magnetic field (RMF) is yet to be deciphered. To provide insights into this important problem, we evaluate the cell death pathway for two magnetic nanocomposites with highly distinct geometries: ZnFeO-PLGA magnetic nanospheres (MNSs) and ZnFeO-PLGA magnetic nanochains (MNCs). We show that under exposure to an RMF, the MNSs and the MNCs exhibit a corkscrewed circular propulsion mode and a steering propulsion mode, respectively. This distinct behavior, with important implications for the associated magneto-mechanical forces exerted by these nanomaterials on surrounding structures (e.g., the cellular membrane), depends on their specific geometries. Next, using numerical simulations and cell viability experiments, we demonstrate that the field strength of the RMF and the rotating speed of the MNSs or MNCs have strong implications for their magneto-mechanical therapeutic performance. Last, we reveal that the magneto-mechanical effects of MNSs are more prone to induce cell apoptosis, whereas those of the MNCs favor instead cell necrosis. Overall, this work enhances the current understanding of the dependences existing between the magneto-mechanical therapeutic effects of magnetic nanocomposites with different geometries and associated cell death pathways, paving the way for novel functionalization routes which could enable significantly enhanced cures and biomedical tools. STATEMENT OF SIGNIFICANCE.