Magneto-Electric Nanoparticles Cobalt Ferrite (CoFe2O4) -- Barium Titanate (BaTiO3) for Non-Invasive Neural Modulations

Abstract

Non-invasive brain stimulation is valuable for studying neural circuits and treating various neurological disorders in human. However, current technologies of noninvasive brain stimulation usually have low spatial and temporal precision and poor brain penetration, which greatly limit their application. A new class of nanoparticles known as magneto-electric nanoparticles (MENs) is highly efficient in coupling an externally applied magnetics wave with generating local electric fields for neuronal activity modulation. Here, a new type of MENs was developed that consisted of CoFe2O4- BaTiO3 and had excellent magneto-electrical coupling properties. Calcium imaging technique was used to demonstrate their efficacy in evoking neuronal activity in organotyic and acute cortical slices that expressed GCaMP6 protein. For in vivo noninvasive delivery of MENs to brain, fluorescently labeled MENs were intravenously injected and attracted to pass through blood brain barrier to a targeted brain region by applying a focal magnet field. Magnetic wave (~450 G at 10 Hz) applied to mouse brain was able to activate cortical network activity, as revealed by in vivo two-photon and mesoscopic imaging of calcium signals at both cellular and global network levels. The effect was further confirmed by the increased number of c-Fos expressing cells after magnetic stimulation. Histological analysis indicated that neither brain delivery of MENs nor the subsequent magnetic stimulation caused any significant increases in the numbers of GFAP and IBA1 positive astrocytes and microglia in the brain. MENs stimulation also show high efficacy in short-term pain relieve when tested with a tibial nerve injury mouse model. The study demonstrates the feasibility of using MENs as a novel efficient and non-invasive technique of brain stimulation, which may have great potential for translation.