Revolutionary Wireless Nanosystem Sparks New Hope in Parkinson’s Care

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Parkinson’s disease (PD) stands as the second prevalent neurodegenerative illness, predominantly marked by motor impairments. Its pathological signature is the abnormal buildup of α-synuclein (α-syn) into insoluble fibrils and Lewy bodies, resulting in the degradation and demise of dopaminergic neurons within the substantia nigra of the midbrain. To alleviate motor symptoms in affected individuals, a widespread clinical method, deep brain stimulation (DBS), entails implanting electrodes into certain brain areas to adjust neuronal activity through direct electrical impulses. 

Though DBS improves the regulation of neuronal activity, its invasive character may cause cognitive deterioration and emotional issues including depression and anxiety. As a consequence, subsequent non-invasive strategies such as transcranial direct current stimulation and transcranial magnetic stimulation can boost cortical responsiveness but are circumscribed by insufficient depth of penetration and spatial resolution. Thus, the development of non-invasive DBS technologies that merge high spatial resolution with robust penetration potential is vital.

In a study released in Science Advances, a team of researchers led by Prof. CHEN Chunying from the National Center for Nanoscience and Technology (NCNST) of the Chinese Academy of Sciences developed a wireless photothermal DBS nanosystem, Au@TRPV1@β-syn nanoparticles (ATB NPs). This system allows for accurate modulation of degenerated neurons by directly stimulating the endogenous expression of the thermosensitive TRPV1 receptor in neurons, thus providing new perspectives on the treatment of PD and other neurodegenerative conditions.

The system is composed of three fundamental modules: a photothermal conversion module (gold nanoshells, i.e., AuNSs) for activating the thermosensitive TRPV1 ion channels; a targeting module (TRPV1 antibody) aimed at specifically identifying dopaminergic neurons with elevated TRPV1 expression; and a degradation module (β-syn peptide, incorporating a near-infrared-responsive linker) that binds to the hydrophobic region of the non-amyloid-β component of α-synuclein, promoting the degradation of α-syn fibrils.

Utilizing an α-syn fibril-induced PD model, the researchers endeavored to regenerate the degenerated dopaminergic neurons in the substantia nigra of the midbrain with the application of the wireless DBS nanosystem.

Following stereotactic injection of ATB NPs into the substantia nigra of PD mice, the nanoparticles adhered to the surface of dopaminergic neurons through the TRPV1 antibody. Under 808 nm pulsed near-infrared laser illumination, they functioned as nanoantennas, transforming light into heat to activate the thermosensitive TRPV1 receptor, leading to Ca2+ influx and the initiation of action potentials. Simultaneously, they released β-syn peptides, which, by activating chaperone-mediated autophagy pathways, eliminated α-syn aggregates, diminishing pathological fibrils. Ultimately, the ATB NPs reinstated the interactive network of dopaminergic neurons and enhanced their dopamine release ability, improving motor functions in PD mice.

This wireless DBS nanosystem presents three key benefits: It utilizes the endogenously expressed TRPV1 receptors in dopaminergic neurons of the substantia nigra, negating the need for implanted neural electrodes or genetic alterations; it allows for precise spatiotemporal control of degenerating neurons in specific brain areas by incorporating near-infrared laser technology; and it demonstrates remarkable biosafety.

Citation: Wu J, Cui X, Bao L, Liu G, Wang X, Chen C. A nanoparticle-based wireless deep brain stimulation system that reverses Parkinson’s disease. Sci Adv. 2025;11(3):eado4927. doi: 10.1126/sciadv.ado4927

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