Modulation of Neural Activity via On-Demand Magnetothermal Drug Release

This project explains the development of a new chemomagnetic platform for the local delivery of dopamine upon exposure to Alternating Magnetic Fields (AMF). The novelty of this project lies on the chemomagnetic material platform, in which the synergy of smart polymers and the magnetothermal properties of magnetic nanoparticles (MNPs) are exploited to develop a biocompatible, wireless, and pharmacologically stable nanotechnology for neuromodulation. MNPs respond to applied untethered, non-ionizing, harmless and tissue penetrable AMF, and transduce them into heat stimulus. MNPs performance in transducing AMF is optimized by controlling its shape, size, and composition. Furthermore, smart polymer coatings undergoing rapid conformational changes in response to an external stimulus such as pH, temperature, ionic strength, or irradiation are of high scientific interest in biomedical research. Here, the reversible thermodynamic behavior of biocompatible poly (oligo ethylene glycol methyl ether methacrylate) (POEGMA) brushes is studied extensively using the Quartz Crystal Microbalance with Dissipation (QCM-D). The reversible thermodynamic phase transition of POEGMA brushes is demonstrated for controlled drug release in multiple doses triggered on-demand by local temperature changes. Spherical iron oxide nanoparticles and POEGMA brushes are utilized in the development of a chemomagnetic system to modulate striatal neuronal circuits, which are known to malfunction during Parkinson's disease. POEGMA brushes are grown from the surface of MNPs. A neurostimulator is encapsulated within the POEGMA coating on the MNPs' surface. Neurostimulator laden MNPs-POEGMA are used to stimulate primary rat neuronal circuits. Upon exposure to AMF, MNPs undergo hysteresis power loss. The local heat dissipated by MNPs triggers a thermodynamic phase transition on the POEGMA brush coating releasing the neurostimulator as a result. Released neurostimulator actuates on specific transmembrane receptors evoking neuronal activity.