Cell-Derived Nano-Ghosts for the Treatment of Brain Disorders

Many central nervous system (CNS) disorders, including neuroinflammatory and malignant diseases, are severely undertreated due to the pharmacological limitations posed by the impermeable blood-brain barrier (BBB). Brain targeted drug delivery systems have been widely investigated as means to overcome the BBB. Despite preclinical success such systems have failed to translate into clinical trials. This is mostly due to their inability to selectively track and target the evolving pathologies of said disorders.

Nano-ghosts (NGs) are nano-vesicles produced from the plasma membrane of human mesenchymal stem cells (MSCs). MSCs were shown to possess membrane-associated targeting and migratory abilities to and through the BBB, and towards sites of inflammation.

The NGs are expected to retain the cell surface moieties and encompass their unique targeting capabilities, and therefore may serve as an effective drug delivery system for targeting neuroinflammatory disorders. Our primary hypothesis is, therefore, that brain targeting of a healthy or diseased BBB can be accomplished by NGs.

Our results show that NGs pass the BBB, both in vitro and in vivo. When NGs were placed on top of an in vitro transwell model of the BBB, their transport was almost identical to that through a control transwell. In vitro results also show that NGs selectively target microglial cells compared to astrocytes. In addition, NGs administered to a mouse model for multiple sclerosis (EAE) selectively accumulated in the animals’ brains and spinal cords and could be detected in and around sclerotic lesions.