Nanoparticle-based deep brain stimulation can treat Parkinson's disease without implanted electrode

With the onset of an aging population, the annual incidence of neurodegenerative conditions such as Parkinson's disease, characterized by the degeneration of nerve cells, is escalating rapidly. One of the various therapeutic approaches for such diseases that is garnering attention is deep brain stimulation, a technique that employs electrical stimulation to directly trigger communication between nerve cells.

Recently, a research team at POSTECH – headed by Professor Won Jong Kim from the Department of Chemistry – developed a new technique for administering electrical stimulation to the brain without the need for implanted electrodes. The findings of this study have been published online in Nature Biomedical Engineering.

Activation of nerve cells through electrode implantation is a treatment option for neuronal disorders, made possible by deep brain stimulation. However, this therapy necessitates a surgical procedure in which leads are deeply implanted into the brain, potentially leading to side effects that can make clinical application challenging. In particular, repeated surgeries due to limited battery life are not only expensive but can result in serious adverse effects, including brain hemorrhage, seizure, and inflammatory responses.

The research team led by Professor Kim aimed to create a nanomedicine material that uses piezoelectricity to produce electrical signals in response to non-invasive and biocompatible ultrasonic waves. Piezoelectric materials can generate voltage through shape deformation caused by physical stimulation, as they induce dielectric polarization from the asymmetric charge distribution in the crystal lattice to the molecule. However, the previously studied piezoelectric materials have been highly cytotoxic and must effectively cross the blood-brain-barrier to reach nerve cells from the bloodstream.

The research team addressed this issue by introducing a polymer material with exceptional biocompatibility, along with nitric oxide, a radical gas molecule naturally present in the body that can facilitate the opening of the blood-brain-barrier.

The team has developed piezoelectric nanoparticles that respond specifically to ultrasonic waves and emit nitric oxide. This temporarily disrupts the blood-brain-barrier, enabling the nanoparticles to accumulate in the brain parenchyma. Additionally, the piezoelectric effect generates a current that induces the release of dopamine in neurons. These nanoparticles have been found to relieve Parkinson's disease symptoms in a mouse model, without causing any toxicity.

This study presents a novel therapy approach for non-invasive treatment of brain diseases. It involves enhancing blood-brain-barrier permeability using nitric oxide, thereby allowing targeted delivery of therapeutic agents. The method's significant advantage lies in the use of high-intensity focused ultrasound, which can serve both as an imaging tool and as a means of releasing nitric oxide to specific areas.

Professor Won Jong Kim of POSTECH stated that the newly created piezoelectric nanoparticle has the potential to non-invasively stimulate deep brain tissues. He further suggested that this strategy could establish a new paradigm for other minimally invasive therapies in the treatment of neurodegenerative diseases.

This study was supported by the National Research Foundation of Korea and OmniaMed Co., Ltd.