GBM-shuttle: glioblastoma blood-brain barrier model for developing nano-shuttles
CBrain tumors have a poor prognosis and are associated with a high morbidity and mortality rate in cancer patients. The blood-brain barrier (BBB) severely limits current therapeutic options, and surgical resection is only feasible for a handful of clinical scenarios. Therefore, there is an urgent need to better understand the relationship between brain tumor and brain capillaries and to develop effective therapeutics. This project aims to develop a novel glioblastoma model integrated into the blood-brain barrier in microfluidic devices and demonstrate how these systems can be used to evaluate BBB-penetrating nanoshuttles to deliver drugs to the brain to treat brain tumors. To achieve this goal, we will use cutting-edge stem cell technologies to develop a human cell- based, physiologically relevant glioblastoma BBB chip model that recapitulates tissue function and microenvironment as in vivo, eliminating many of the consequences observed in animal models and allowing us to achieve better translational outcomes for the clinic. We will search for peptides that target highly expressed proteins on brain endothelia and exhibit transcytosis activity. By developing new nano-shuttle systems coated with peptides that penetrate the BBB, we will deliver drugs to the brain at effective therapeutic concentrations while avoiding unwanted side effects.
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