Ultrasound-Triggered Biomimetic Piezo-Nanoplatforms for Non-Invasive Epilepsy Treatment

Epilepsy is one of the most prevalent central nervous system disorders, with antiepileptic drugs (AEDs) as the mainstay of treatment. While effective in reducing seizure frequency in ≈70% of patients, traditional AEDs are limited by blood concentration fluctuations, drug resistance, and cognitive side effects. Neuromodulation, particularly electrical stimulation, has emerged as a promising alternative by reversibly regulating abnormal neural circuits. However, conventional systems require implanted electrodes and external power sources, increasing the risk of trauma and infection. Piezoelectric nanomaterials offer a non-invasive strategy by converting endogenous biomechanical forces or ultrasound stimulation into localized electric currents, inducing neuronal hyperpolarization to suppress excitation. Based on this mechanism, a biomimetic piezoelectric nanoplatform is developed capable of ultrasound-triggered electrical stimulation for targeted neuromodulation without surgical implantation. Additionally, these nanoplatforms can co-deliver AEDs, enabling a dual therapeutic approach that combines localized stimulation with sustained drug release, enhancing efficacy while minimizing systemic exposure. This synergistic integration of ultrasound-responsive piezoelectric nanoplatforms and pharmacotherapy represents a transformative paradigm for safe, effective, and non-invasive epilepsy treatment.