Nano-magnetoelectric biomimetic system promotes neural differentiation and reverses dopaminergic neuron damage for Parkinson's disease therapy

Parkinson's disease (PD), a neurodegenerative disorder characterized by the depletion of dopaminergic neurons, has conventionally been managed through pharmacological intervention and deep brain stimulation (DBS) surgery. However, drug resistance and the risks of surgical implantation have hindered the effective of current treatment. Herein, we endeavor to engineer a wireless, non-invasive nanoplatform for electrostimulation-enhanced drug therapy, termed BCFO@LCM. This innovative platform integrates magnetoelectric nanomaterials (BaTiO 3 -CoFe 2 O 4 ) encapsulated within BV2 cell membranes (CM), enabling traversal of the blood-brain barrier (BBB) and dual-targeting of the PD microenvironment through magnetic and membrane fusion mechanisms. When exposed to an external magnetic field, this system facilitates the controlled release of the therapeutic agent L-DOPA for pharmacotherapy, concurrently generating electrical signals via the magnetoelectric nanomaterials to effectuate neuromodulation. Our findings reveal that BCFO@LCM markedly ameliorates dyskinesia in PD model mice, diminishes the attrition of dopaminergic neurons in the substantia nigra and striatum, augments tyrosine hydroxylase levels, and ultimately reverses the damage to dopaminergic neurons. Furthermore, the non-invasive electrical stimulation enhances neuronal activity within deep brain tissues and fosters the regeneration and differentiation of neurons.