BME 7900: "Highly penetrative nanocarriers loaded with drugs targeted to resistant cells improve treatment of brain tumors"
BME 7900 Seminar Series talk by Mark Saltzman, Yale University.
Current therapy for malignant brain tumors, such as glioblastoma multiforme (GBM), is insufficient, with nearly universal recurrence. Available drug therapies are unsuccessful because they fail to penetrate through the region of the brain containing tumor cells and they fail to kill the cells most responsible for tumor development and therapy resistance, brain cancer stem cells (BCSCs). To address these challenges, we combined two advances in technology: 1) brain-penetrating polymeric nanoparticles that can be loaded with drugs and are optimized for intracranial convection-enhanced delivery (CED); and 2) re-purposed, FDA-approved compounds, which were identified through library screening to target BCSCs. Using fluorescence imaging and positron emission tomography (PET), we demonstrate that brain-penetrating nanoparticles can be delivered intracranially to large volumes in both rat and pig. We identified several FDA-approved agents that potently inhibit proliferation and self-renewal of BCSCs. When loaded into brain-penetrating nanoparticles and administered by CED, one of these agents significantly increased survival in rats bearing BCSC-derived xenografts. This new approach to controlled delivery in the brain should have a significant impact on treatment of GBM and suggests new routes for drug and gene delivery to treat other diseases of the CNS.
