This work investigates the thermodynamic phase transition of poly(oligo(ethylene glycol)methyl ether methacrylate) brushes using the quartz crystal microbalance with dissipation for applications in programmable and controllable drug delivery.

Noninvasive manipulation of cell signaling is critical in basic neuroscience research and in developing therapies for neurological disorders and psychiatric conditions. Here, the wireless force-induced stimulation of primary neuronal circuits through mechanotransduction mediated by magnetic microdiscs (MMDs) under applied low-intensity and low-frequency alternating magnetic fields (AMFs), is described. MMDs are fabricated by top-down lithography techniques that allow for cost-effective mass production of biocompatible MMDs with high saturation and zero magnetic magnetic moment at remanence. MMDs are utilized as transducers of AMFs into mechanical forces. When MMDs are exposed to primary rat neuronal circuits, their magneto-mechanical actuation triggers the response of specific mechanosensitive ion channels expressed on the cell membranes activating ≈50% of hippocampal and ≈90% of cortical neurons subjected to the treatment. Mechanotransduction is confirmed by the inhibition of mechanosensitive transmembrane channels with Gd 3+ . Mechanotransduction mediated by MMDs cause no cytotoxic effect to neuronal cultures. This technology fulfills the requirements of cell-type specificity and weak magnetic fields, two limiting factors in the development of noninvasive neuromodulation therapies and clinical equipment design. Moreover, high efficiency and long-lasting stimulations are successfully achieved. This research represents a fundamental step forward for magneto-mechanical control of neural activity using disc-shaped micromaterials with tailored magnetic properties.

Magnetic hyperthermia has been studied for the past two decades in cancer treatments as the local heat generated by magnetic nanoparticles under applied alternating magnetic fields is sufficient to kill cancer cells. More recently, it has been explored for controlling biological signaling through heat-sensitive transmembrane channels. It is of great interest to produce magnetic nanoparticles with high heat transducing efficiency to minimize potential off-target heating effects. Here, we describe shape anisotropy and particle hybridization as possible routes to augment magnetic hyperthermia in ferrite nanoparticles. Zinc substituted magnetite core and core-shell cubic nanoparticles with different sizes were synthetized. It was found that nanoparticles shape and composition are altered from cubic to flower-like, and to a more franklinite rich phase as size increased. Hybridization with a cobalt shell allowed to enhance nanoparticle magnetic coercivity and specific power loss. The optimized core-shell nanoparticles were tested to induce cellular activity in hippocampal neurons.

Minimally invasive manipulation of cell signaling is critical in basic neuroscience research and in developing therapies for neurological disorders. Here, a wireless chemomagnetic neuromodulation platform for the on-demand control of primary striatal neurons that relies on nanoscale heating events is described. Iron oxide magnetic nanoparticles (MNPs) are functionally coated with thermoresponsive poly (oligo (ethylene glycol) methyl ether methacrylate) (POEGMA) brushes loaded with dopamine. Dopamine loaded MNPs-POEGMA are co-cultured with primary striatal neurons. When alternating magnetic fields (AMF) are applied, MNPs undergo hysteresis power loss and dissipate heat. The local heat produced by MNPs initiates a thermodynamic phase transition on POEGMA brushes resulting in polymer collapse and dopamine release. AMF-triggered dopamine release enhances the response of dopamine ion channels expressed on the cell membranes enhancing the activity ≈50% of striatal neurons subjected to the treatment. Chemomagnetic actuation on dopamine receptors is confirmed by blocking D 1 and D 2 receptors. The reversible thermodynamic phase transition of POEGMA brushes allow the on-demand release of dopamine in multiple microdoses. AMF-triggered dopamine release from MNPs-POEGMA causes neither cell cytotoxicity nor promotes cell reactive oxygen species production. This research represents a fundamental step forward for the chemomagnetic control of neural activity using hybrid magnetic nanomaterials with tailored physical properties.