A Nanoparticle-Based Wireless Deep Brain Stimulation System that Reverses Parkinson’s Disease

Deep brain stimulation (DBS) technology enables the neural modulation with precise spatial control, but requires permanent implantation of conduits. Here, we describe a photothermal wireless DBS nanosystem capable of eliminating α-synuclein (α-syn) aggregates and restoring degenerated dopamine neurons in the substantia nigra (SN) to treat Parkinson’s disease (PD). This nanosystem (ATB NPs) consist of Au nanoshell, an antibody against the heat-sensitive receptor TRPV1, and β-synuclein (β-syn) peptides with a NIR-responsive linker. ATB NPs by stereotactic injection target dopamine neurons expressing TRPV1 receptors in the SN. Upon pulsed NIR irradiation, ATB NPs, serving as nanoantennae, convert the light into heat, leading to calcium ion influx, depolarization, and action potentials in dopamine neurons through TRPV1 receptors. Simultaneously, β-syn peptides released from ATB NPs cooperate with chaperone mediated autophagy initiated by heat shock protein, HSC70, to effectively eliminate α-syn fibrils in neurons. These orchestrated actions restored pathological dopamine neurons and locomotor behaviors of PD.