Recently, a research team led by Prof. CHEN Chunying from the National Center for Nanoscience and Technology (NCNST) of the Chinese Academy of Sciences (CAS) revealed that a nanoparticle-based wireless deep brain stimulation system that reverses Parkinson’s Disease. Related research was published in Science Advances.
Parkinson's Disease (PD) is the second most common neurodegenerative disorder after Alzheimer's Disease, primarily characterized by motor dysfunction. The pathological hallmark of PD is the abnormal aggregation of α-synuclein (α-syn) into insoluble fibrils and Lewy bodies, leading to the degeneration and death of dopaminergic neurons in the substantia nigra of the midbrain. Currently, to ameliorate motor symptoms in patients, a common clinical approach involves the implantation of electrodes into specific brain regions to modulate neuronal activity through direct electrical stimulation. Although this method, known as Deep Brain Stimulation (DBS), enhances the efficiency of neuronal regulation, its invasive nature can lead to cognitive decline and emotional disturbances, such as depression and anxiety. Subsequently developed non-invasive techniques, such as transcranial direct current stimulation and transcranial magnetic stimulation, can enhance cortical excitability but are limited by insufficient penetration depth and spatial resolution, making precise modulation of deep brain regions challenging. Therefore, the development of non-invasive deep brain stimulation technologies that combine high spatial resolution with strong penetration capabilities is crucial.
In this work, the research team designed a wireless photothermal DBS nanosystem, named ATB NPs. This system achieves precise modulation of degenerated neurons by directly stimulating the endogenous expression of the thermosensitive TRPV1 receptor in neurons. The system consists of three core modules: a photothermal conversion module (gold nanoshells, 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, thereby degrading α-syn fibrils.
After stereotactic injection of ATB NPs into the substantia nigra of PD mice, the ATB NPs anchor to the surface of dopaminergic neurons via the TRPV1 antibody. Under 808 nm pulsed near-infrared laser irradiation, the ATB NPs act as nanoantennas, converting light into heat to activate the thermosensitive TRPV1 receptor, leading to Ca2+ influx and the generation of action potentials. Simultaneously, the ATB NPs release β-syn peptides, which, through the activation of chaperone-mediated autophagy pathways, clear α-syn aggregates, thereby reducing pathological fibrils. Ultimately, the ATB NPs restore the interactive network of dopaminergic neurons and their dopamine release capacity, improving motor function in PD mice.
The advantages of this wireless DBS nanosystem primarily include the following: 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 the wireless DBS nanosystem exhibits excellent biosafety. Prof. CHEN Chunying believes that this nanoparticle-based wireless DBS therapeutic strategy offers a novel approach for the treatment of Parkinson's Disease and other neurodegenerative disorders.
Figure. A nanoparticle-based wireless deep brain stimulation system that reverses parkinson’s disease.
(Image by CHEN Chunying et al)
Contact:
CHEN Chunying
National Center for Nanoscience and Technology (NCNST)
E-mail: chenchy@nanoctr.cn
