Glioblastoma, the most common adult brain tumor, is among the deadliest of all solid tumors with a median survival of 14.6 months. This status has not changed for over ten years despite intense therapeutic efforts. A unique and major challenge in treating brain tumors is difficulty in delivering effective drugs across the blood-brain barrier (BBB), which protects the brain by preventing many substances in the blood from entering the brain tissue. Our long-term goal is to develop a strategy to temporarily increase BBB permeability and allow effective delivery of anti-cancer drugs without causing additional damage to the brain. This project aims to design and produce magnetic nanoparticles th...

Read More

Glioblastoma, the most common adult brain tumor, is among the deadliest of all solid tumors with a median survival of 14.6 months. This status has not changed for over ten years despite intense therapeutic efforts. A unique and major challenge in treating brain tumors is difficulty in delivering effective drugs across the blood-brain barrier (BBB), which protects the brain by preventing many substances in the blood from entering the brain tissue. Our long-term goal is to develop a strategy to temporarily increase BBB permeability and allow effective delivery of anti-cancer drugs without causing additional damage to the brain. This project aims to design and produce magnetic nanoparticles that target endothelial cell tight junction-associated proteins, which form a critical component of the blood-brain barrier. By using a pulsed magnetic field, we will remotely stimulate the blood vessel component by a magnetomechanical mechanism and temporarily render the BBB permeable to circulating drugs with short-term magnetic heating. This combined molecular – nanotechnology approach greatly contrasts with previous methods relying on non-specific osmotic forces to disrupt the BBB, which have been abandoned due to the high toxicity to the brain. This approach is different from the more modern technique of using ultrasound and microbubbles, which stretches blood vessels to increase permeability and can damage the tissue. In addition, there would be advantages in penetrating deeper into the brain with magnetic field compared with ultrasound. We will test our hypothesis using both a healthy brain as well as tumor-bearing brain in rodent models. Success of this work would provide significant conceptual and technological advances for brain tumor drug delivery. The ability to trigger temporary BBB opening for improved delivery of therapies in the bloodstream could increase survival for brain tumor patients after years of disappointment.

Read Less