The Blood-Brain Barrier high selectivity (BBB) restricts the delivery of an adequate amount of drugs to the brain in case of diseases such as Glioblastoma (GBM). To overcome this obstacle, our lab developed a novel delivery system, termed Nano-Ghosts (NG). The NGs are Nano-vesicles produced from the plasma membrane of human Mesenchymal Stem Cells (hMSCs). In this study, we aimed to utilize the NGs as an effective drug delivery system for the treatment of GBM, hypothesizing that NGs would actively transport across the BBB and specifically target the tumor site. Our in-vivo studies using U87 intracranial tumor model showed that following IV injection, the NGs penetrate to the brain and particularly accumulate in the tumor site. This result was repeated in a mouse model of intracranial 005 cells injection that was performed in collaboration with Prof. Dinorah Fridman-Morvinski from Tel-Aviv University. Furthermore, we loaded the NGs with Gboxin, and the bioactivity of Gboxin-NGs was tested in-vivo, where the Gboxin-NGs significantly reduced the tumor size and prolonged animal survival compared to the free drug. In addition, we have engineered NGs to present on their membranes PD-1 protein, which is an immune checkpoint blockade, disrupting the PD-1/PD-L1 and, consequently, boosting the immune system response. These PD1-NGS reduced tumor size and improved animal survival. Altogether, in this research, we showed NGs effectiveness as a versatile targeted drug-delivery system for the treatment of GBM.