Delivering MicroRNA‐137 to the Brain via Nanoparticles

Abstract

Genetic mutations of microRNA‐137 (miR‐137) are strongly associated with symptoms of schizophrenia. Elevated miR‐137 impairs neuronal, dendritic, and synaptic development. Additionally, miR‐137 regulates multiple key mRNA transcripts that are critical for cognitive and sensory processing, and that are common genes dysregulated in schizophrenia. However, there remains a major barrier to treatment of schizophrenia due to the lack of targeted delivery of effective therapeutics to the brain. Encapsulating miR‐137 in nanoparticles offers a drug delivery system that can pass the blood‐brain‐barrier, allowing miR‐137 to have effects in the brain. We hypothesize that inhibiting endogenous levels of miR‐137, with the antisense sequence (anti‐miR‐137), may improve neurobiological and behavioral deficits as a result of miR‐137 overexpression. We encapsulated miR‐137 in nanoparticles and analyzed the size, polydispersity index, zeta potential, uptake efficiency, cargo delivery, and toxicity of miR‐137 loaded nanoparticles after treatment in cell culture. Results indicate nanoparticles are nontoxic delivery vehicles and are easily incorporated into cells. Additionally, the miR‐137 cargo is released from the nanoparticles and is detected as elevated miR‐137 levels. Following in vitro studies, we will test the most efficient delivery method to deliver nanoparticles to the brain in vivo by florescent labeling and ex vivo nanoparticle tracking. Delivering therapeutic RNAs to the brain will improve targeted drug delivery systems for central nervous system disorders.