A novel wireless photothermal DBS nanosystem uses nanoparticles to target and restore damaged neurons in Parkinson’s disease, offering a non-invasive, precise, and safe alternative to traditional DBS.
Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder, primarily marked by motor dysfunction. The pathological hallmark of PD is the abnormal aggregation of α-synuclein (α-syn) into insoluble fibrils and Lewy bodies, which causes the degeneration and death of dopaminergic neurons in the substantia nigra of the midbrain.
Deep brain stimulation (DBS), a widely used clinical intervention to alleviate motor symptoms, involves implanting electrodes in specific brain regions to modulate neuronal activity via direct electrical stimulation.
While DBS improves neuronal regulation, its invasive nature can result in side effects, including cognitive decline and emotional disturbances such as depression and anxiety. To address these challenges, non-invasive techniques like transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) have been developed. These methods enhance cortical excitability but are limited by insufficient penetration depth and low spatial resolution. Consequently, advancing non-invasive DBS technologies that integrate high spatial resolution with strong penetration capabilities remains a critical goal.
A Novel Approach: Wireless Photothermal DBS Nanosystem
In a study published in Science Advances, a research team led by Prof. Chunying Chen from the National Center for Nanoscience and Technology (NCNST) of the Chinese Academy of Sciences designed a wireless photothermal DBS nanosystem, Au@TRPV1@β-syn nanoparticles (ATB NPs).
This system achieves precise modulation of degenerated neurons by directly stimulating the endogenous expression of the thermosensitive TRPV1 receptor in neurons, thereby offering new insights into the treatment of PD and other neurodegenerative disorders.
This system consists of three core modules: a photothermal conversion module (gold nanoshells, i.e., AuNSs) for activating the thermosensitive TRPV1 ion channels; a targeting module (TRPV1 antibody) to specifically target dopaminergic neurons with high TRPV1 expression; and a degradation module (β-syn peptide, containing a near-infrared-responsive linker) that binds to the hydrophobic domain of the non-amyloid-β component of α-synuclein, facilitating the degradation of α-syn fibrils.
Mechanism and Results in Parkinson’s Disease Model
Using an α-syn fibril-induced PD model, the researchers attempted to restore the degenerated dopaminergic neurons in the substantia nigra of the midbrain through the use of the wireless DBS nanosystem.
After stereotactic injection of ATB NPs into the substantia nigra of PD mice, the nanoparticles anchored to the surface of dopaminergic neurons via the TRPV1 antibody. Under 808 nm pulsed near-infrared laser irradiation, they functioned as nanoantennas, converting light into heat to activate the thermosensitive TRPV1 receptor, leading to Ca2+ influx and the generation of action potentials. Meanwhile, they released β-syn peptides, which, through the activation of chaperone-mediated autophagy pathways, cleared α-syn aggregates, reducing pathological fibrils. Ultimately, the ATB NPs restored the interactive network of dopaminergic neurons and their dopamine release capacity, improving motor function in PD mice.
This wireless DBS nanosystem has three primary advantages: It leverages the endogenously expressed TRPV1 receptors in dopaminergic neurons of the substantia nigra, eliminating the need for implanted neural electrodes or genetic manipulation; it enables precise spatiotemporal modulation of degenerative neurons in specific brain regions by integrating near-infrared laser technology; and it exhibits excellent biosafety.
Reference: “A nanoparticle-based wireless deep brain stimulation system that reverses Parkinson’s disease” by Junguang Wu, Xuejing Cui, Lin Bao, Guanyu Liu, Xiaoyu Wang and Chunying Chen, 15 January 2025, Science Advances.
DOI: 10.1126/sciadv.ado4927
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