Nano-ghosts for drug transport across the blood-brain barrier

Introduction: The Blood-Brain Barrier (BBB) protect the central nervous system (CNS)from blood fluctuation and toxic substance. Unfortunately, the high selectivity of the BBB restricts the delivery of drugs to the brain1. Therefore, in case of illness such as glioblastoma appropriate therapy cannot be delivered. To overcome this barrier our lab developed a novel delivery system, Nano-Ghosts (NG). The NGs are Nano-vesicles produced from the plasma membrane of human Mesenchymal Stem Cells (hMSCs)2. 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 study with U87 intracranial model injection showed the NGs penetrate to the brain and particularly colocalize in the tumor site after one week of NGs IV injection. This result was repeated in a mouse model of intracranial 005 cells injection that was done with the collaboration of Dr. Dinorah Fridman-Morvinski from Tel-Aviv university. In addition, to study the ability of the NGs to serve as an effective drug delivery we encapsulate Gboxin inside the NG during the NGs preparation and the toxicity of Gboxin-NGs was measured on glioma cells and brain cells in-vitro. Gboxin-NGs induced apoptosis in U87 cells while for cortical neuron and glia cells we almost didn’t observe any apoptosis. This result correlates with previous in-vitro targeting studies in which NG targeting towards U87 was higher when compared to the healthy brain cells.

Conclusion: We showed in-vivo the ability of the NG to overcome the BBB barrier and accumulate in the tumor site and proved in-vitro the NGs effectiveness as targeted drug-delivery system against glioma cells.

1.Jamieson, J. J., Searson, P. C. & Gerecht, S. Engineering the human blood-brain barrier in vitro. J. Biol. Eng. 11, 1–11 (2017).

2. Toledano Furman, N. E. et al. Reconstructed stem cell nanoghosts: A natural tumor targeting platform. Nano Lett. 13, 3248–3255 (2013).