MOF-based nanoparticles enabling blood-brain barrier crossing for non-invasive selective sononeuromodulation in...

Epilepsy affects millions worldwide, with a significant proportion of patients exhibiting resistance to conventional pharmacological treatments, highlighting the urgent need for innovative, non-invasive therapeutic strategies. Traditional electrical neuromodulation methods, such as deep brain stimulation, are hindered by their invasiveness, limited spatial precision, and associated risks of infection. In this study, we develop an ultrasound (US)-activated piezoelectric nanoparticle platform (PUANPs), based on a metal-organic framework, to enable precise and non-invasive neuromodulation for epilepsy management. Upon US stimulation, PUANPs convert mechanical energy into localized electrical signals, effectively modulating neuronal activity by enhancing inhibitory signaling and suppressing excitatory responses. Functionalized with brain-targeting ligands, PUANPs achieve efficient blood-brain barrier (BBB) penetration via receptor-mediated transport and US-induced cavitation. Furthermore, the incorporation of platinum nanoclusters enhances piezoelectric performance while concurrently attenuating neuroinflammation and oxidative stress in epileptic foci. By integrating neuromodulation, targeted BBB crossing, and microenvironmental regulation, PUANPs represent a multifunctional therapeutic approach that surpasses the limitations of conventional treatments and holds broad translational potential for epilepsy therapy.