Biomimetic Piezoelectric Nanoparticles for Targeted Ultrasound-Driven Neuromodulation and Precise Neurotransmitter Release

Electrical stimulation serves as a fundamental tool for neuromodulation. Piezoelectric nanomaterials have become a central focus in wireless, battery-free electrical stimulation, which holds great promise for modulating neural circuits and treating neurological disorders. However, ultrasound-activated piezoelectric stimulation remains limited by off-target effects, low spatial precision, and inefficient energy transfer. Here, we developed a cell-targeting neuromodulation strategy using L-Dopa-coated barium titanate nanoparticles (BT-Dopa NPs). The biomimetic L-Dopa coating significantly enhances nanoparticle dispersibility and improves neuronal targeting efficiency. Under ultrasound excitation, these BT-Dopa NPs generate localized electrical currents that effectively stimulate Ca2+ influx and trigger the release of key catecholamine neurotransmitters, including dopamine and norepinephrine, from PC 12 cells. This on-demand stimulation was achieved without inducing significant cytotoxicity, providing a minimally invasive platform for precise neural circuit modulation.