Brain tumors are known to be lethal, with a median survival of 14.6 months for glioblastoma multiforme. A major and unique obstacle for brain tumor drug delivery is the presence of blood-brain barrier (BBB). The BBB is a complex protein structure associated with cerebral capillaries, which prevent entry of even the smallest molecules into the brain parenchyma, thereby severely limiting evaluation of potentially efficacious anti glioma therapies. The goal of our project is to develop a novel approach to optically open the BBB thus allowing the access of a wide range of therapeutic drugs to brain tumor cells. We propose to temporarily open the BBB by targeting nanoparticles to the cell-to-ce...

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Brain tumors are known to be lethal, with a median survival of 14.6 months for glioblastoma multiforme. A major and unique obstacle for brain tumor drug delivery is the presence of blood-brain barrier (BBB). The BBB is a complex protein structure associated with cerebral capillaries, which prevent entry of even the smallest molecules into the brain parenchyma, thereby severely limiting evaluation of potentially efficacious anti glioma therapies. The goal of our project is to develop a novel approach to optically open the BBB thus allowing the access of a wide range of therapeutic drugs to brain tumor cells. We propose to temporarily open the BBB by targeting nanoparticles to the cell-to-cell junctions of the tumor vasculature. First, we will determine the minimal nanoparticle and laser dose that lead to BBB opening and develop biodegradable polymers that can carry light into precise and deep brain tissues. Second, we will study how the brain responds to the BBB opening at the molecular and cellular levels, in order to ensure safety of the procedure. Lastly, we will use animal brain tumor models to evaluate the extent that BBB opening can help deliver anticancer drugs. This proposed research will allow us to test nanobubble-induced BBB opening with optical resolution to investigate treating infiltrating margins of GBM. Once validated, we will further engage a multidisciplinary team of researchers include clinical MR imaging, veterinary medicine, and neurosurgeons to (1) investigate the possibility of performing BBB opening and drug release simultaneously by nanoparticle carriers; (2) study the in vivo kinetics of BBB transient opening for spontaneous tumor in larger animals (i.e. canine); and (3) explore possibility for clinical trials.

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