Synergistic NIR-polydopamine nanotherapy for blood–brain barrier crossing and Parkinson's disease intervention

Abstract

Despite its clinical success, conventional deep-brain stimulation (DBS) for Parkinson's remains limited by its invasive nature. To overcome this, we engineered ZnO@polydopamine (ZnO@PDA) nanocomposites as a non-invasive neurotherapeutic platform. By leveraging rational nanostructure design, ZnO@PDA enabled reversible blood–brain barrier (BBB) opening via a photothermal mechanism, thereby permitting targeted nanoparticle delivery. Upon reaching the brain, nanocomposites harness ultrasound-driven electrical stimulation to precisely modulate neuronal circuits, thus offering a groundbreaking alternative to traditional DBS. Simultaneously, their potent antioxidant activity neutralizes reactive oxygen species, suppresses microglial overactivation, and mitigates pathological α-synuclein aggregation. In vivo studies demonstrated that laser-triggered ZnO@PDA treatment significantly restored dopaminergic neuronal function and improved motor coordination, whereas ultrasound-based protocols alone were less effective owing to insufficient BBB penetration. Our work presents a “penetration–accumulation–stimulation” cascade strategy, delivering a transformative approach to non-invasive treatment of neurodegenerative disorders.