Nano-Ghosts for Selective Drug Delivery to and Across the Blood Brain Barrier as a Potential Therapy for Glioblastoma Multiforme

The central nervous system (CNS) is protected by the blood–brain barrier (BBB). The BBB, which is formed by impermeable tight junctions (TJs) between Brain Capillary Endothelial cells (BCEC), serves as an active and selective barrier regulating the homeostasis of the brain and protecting it from toxic substances. Unfortunately, the high selectivity of the BBB also hampers the passage of drugs. Despite the rapid development of drugs with well-established activity in the brain, many disorders such as Alzheimer`s disease (AD), Parkinson`s disease (PD), brain tumors and Multiple Sclerosis (MS) remain severely undertreated.

In order to overcome these limitations, we aim to modify our mesenchymal stem cell (MSC) nano-ghosts (NGs) drug delivery system to allow transport across the BBB. The NGs are nano-vesicles produced from the plasma membrane of human mesenchymal stem cells (hMSCs) which possess membrane-associated targeting and migratory abilities to and through the BBB, and towards sites of inflammation. The NGs are expected to retain the cells` surface moieties and encompass their unique targeting capabilities, and therefore may serve as an effective drug delivery system for targeting neurological disorders. Our primary hypothesis is therefore that brain targeting of a healthy or diseased BBB can be accomplished by NGs. The hypothesis will be tested both in vitro, using a 3D model of the BBB, which is composed of a co-culture of rat glial cells and bovine Brain Capillary Endothelial Cells (BCEC), and in vivo, using mice with glioblastoma multiforme (GBM)—an aggressive brain tumor.