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

Abstract 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.