Abstract
Deep brain stimulation technology enables the neural modulation with precise spatial control but requires permanent implantation of conduits. Here, we describe a photothermal wireless deep brain stimulation nanosystem capable of eliminating α-synuclein aggregates and restoring degenerated dopamine neurons in the substantia nigra to treat Parkinson's disease. This nanosystem (ATB NPs) consists of gold nanoshell, an antibody against the heat-sensitive transient receptor potential vanilloid family member 1 (TRPV1), and β-synuclein (β-syn) peptides with a near infrared-responsive linker. ATB NPs by stereotactic injection target dopamine neurons expressing TRPV1 receptors in the substantia nigra. Upon pulsed near-infrared 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-synuclein peptides released from ATB NPs cooperate with chaperone-mediated autophagy initiated by heat shock protein, HSC70, to effectively eliminate α-synuclein fibrils in neurons. These orchestrated actions restored pathological dopamine neurons and locomotor behaviors of Parkinson's disease.