Recent advancements in brain stimulation and nanomedicine have ushered in a new era of therapeutic interventions for psychiatric and neurodegenerative disorders. This review explores the cutting-edge innovations in brain stimulation techniques, including their applications in alleviating symptoms of main neurodegenerative disorders and addiction. Deep Brain Stimulation (DBS) is an FDA-approved treatment for specific neurodegenerative disorders, including Parkinson\'s Disease (PD), and is currently under evaluation for other conditions, such as Alzheimer\'s Disease. This technique has facilitated significant advancements in understanding brain electrical circuitry by enabling targeted brain stimulation and providing insights into neural network function and dysfunction. In reviewing DBS studies, this review places particular emphasis on the underlying main neurotransmitter modifications and their specific brain area location, particularly focusing on the dopaminergic system, which plays a critical role in these conditions. Furthermore, this review delves into the groundbreaking developments in nanomedicine, highlighting how nanotechnology can be utilized to target aberrant signaling in neurodegenerative diseases, with a specific focus on the dopaminergic system. The discussion extends to emerging technologies such as magnetoelectric nanoparticles (MENPs), which represent a novel intersection between nanoformulation and brain stimulation approaches. These innovative technologies offer promising avenues for enhancing the precision and effectiveness of treatments by enabling the non-invasive, targeted delivery of therapeutic agents as well as on-site, on-demand stimulation. By integrating insights from recent research and technological advances, this review aims to provide a comprehensive understanding of how brain stimulation and nanomedicine can be synergistically applied to address complex neuropsychiatric and neurodegenerative disorders, paving the way for future therapeutic strategies.

Core-shell magnetoelectric nanoparticles (MENPs) have recently gained popularity thanks to their capability in inducing a local electric polarization upon an applied magnetic field and vice versa. This work estimates the magnetoelectrical behavior, in terms of magnetoelectric coupling coefficient (αME), via finite element analysis of MENPs with different shapes under either static (DC bias) and time-variant (AC bias) external magnetic fields. With this approach, the dependence of the magnetoelectrical performance on the MENPs geometrical features can be directly derived. Results show that MENPs with a more elongated morphology exhibits a superior αME if compared with spherical nanoparticles of similar volume, under both stimulation conditions analyzed. This response is due to the presence of a larger surface area at the interface between the magnetostrictive core and piezoelectric shell, and to the MENP geometrical orientation along the direction of the magnetic field. These findings pave a new way for the design of novel high-aspect ratio magnetic nanostructures with an improved magnetoelectric behaviour.

Electrical stimulation is regarded pivotal to promote repair of nerve injuries, however, failed to get extensive application in vivo due to the challenges in noninvasive electrical loading accompanying with construction of biomimetic cell niche. Herein, a new concept of magneto responsive electric 3D matrix for remote and wireless electrical stimulation is demonstrated. By the preparation of magnetoelectric core/shell structured Fe3 O4 @BaTiO3 NPs-loaded hyaluronan/collagen hydrogels, which recapitulate considerable magneto-electricity and vital features of native neural extracellular matrix, the enhancement of neurogenesis both in cellular level and spinal cord injury in vivo with external pulsed magnetic field applied is proved. The findings pave the way for a novel class of remote controlling and delivering electricity through extracellular niches-mimicked hydrogel network, arising prospects not only in neurogenesis but also in human-computer interaction with higher resolution.

The brain is a massive network of neurons which are interconnected through chemical and electrical field oscillations. It is hard to overestimate the significance of the ability to control chemical and physical properties of the network at both the collective and single-cell levels. Most psychiatric and neurodegenerative diseases are typically characterized by certain aberrations of these oscillations. Recently, magnetoelectric nanoparticles (MENs) have been introduced to achieve the desired control. MENs effectively enable wirelessly controlled nanoelectrodes deep in the brain. Although MENs have been shown to cross the blood-brain barrier via intravenous (IV) administration, achieving adequate efficacy of the delivery remains an open question. Herein, through in vivo studies on a mouse model, we demonstrate at least a 4-fold improved efficacy of the targeted delivery of MENs across BBB via intranasal administration compared to an equivalent IV administration.

OBJECTIVE: The biodistribution and clearance of magnetoelectric nanoparticles (MENs) in a mouse model was studied through electron energy dispersive spectroscopy.
METHODS: This approach allows for detection of nanoparticles (NPs) in tissues with the spatial resolution of scanning electron microscopy, does not require any tissue-sensitive staining and is not limited to MENs.
RESULTS: The size-dependent biodistribution of intravenously administrated MENs was measured in vital organs such as the kidneys, liver, spleen, lungs and brain at four different postinjection times including 1 day, 1 week, 4 and 8 weeks, respectively.
CONCLUSIONS: The smallest NPs, 10-nm MENs, were cleared relatively rapidly and uniformly across the organs, while the clearance of the larger NPs, 100- and 600-nm MENs, was highly nonlinear with time and nonuniform across the organs.

OBJECTIVE: The in vivo study on imprinting control region mice aims to show that magnetoelectric nanoparticles may directly couple the intrinsic neural activity-induced electric fields with external magnetic fields.
METHODS: Approximately 10 µg of CoFe2O4-BaTiO3 30-nm nanoparticles have been intravenously administrated through a tail vein and forced to cross the blood-brain barrier via a d.c. field gradient of 3000 Oe/cm. A surgically attached two-channel electroencephalography headmount has directly measured the modulation of intrinsic electric waveforms by an external a.c. 100-Oe magnetic field in a frequency range of 0-20 Hz.
RESULTS: The modulated signal has reached the strength comparable to that due the regular neural activity.
CONCLUSIONS: The study opens a pathway to use multifunctional nanoparticles to control intrinsic fields deep in the brain.