Nano-Ghosts for Drug Transport across the Blood-Brain Barrier for the treatment of Glioblastoma

Introduction: The Blood-Brain Barrier high selectivity restrict the delivery of an adequate amount of drugs to the brain1 in case of illness such as Glioblastoma (GBM). To overcome this obstacle our lab developed a novel delivery system, Nano-Ghosts (NG). The NGs are Nano-vesicles produced from the plasma membrane of human Mesenchymal Stem Cells2. In this study, we aim to utilize the NGs as an effective drug delivery system for the treatment of GBM as it can overcome the natural barrier and specifically target the tumor site.

Results: In-vivo studies with U87 intracranial model injection showed the NGs penetrates to the brain and particularly colocalize in the tumor site after NGs IV injection. This result was repeated in a mouse model of intracranial 005 cells injection in collaboration of Dr. Dinorah Fridman-Morvinski from Tel-Aviv university. Furthermore, we loaded Gboxin inside the NGs and the bioactivity of Gboxin-NGs was tested in-vivo. Gboxin-NGs significantly reduced the tumor size and prolonged animal survival compared to the free drug. In addition, we armed the NGs surface by engineering NGs to present PD-1 protein on the membrane. This created an immune checkpoint blockade by disrupting the PD-1/PD-L1 axis to boost the immune system response. PD-1 NGS reduced tumor size and improved animal survival.

Conclusion: We successfully proved NGs effectiveness as a versatile targeted drug-delivery system for the treatment of GBM.