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 major 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) repurposed, FDA-approved compounds, which were identified through library screening to target BSCSs. Using fluorescence imaging and positron emission tomography (PET), we demonstrate that brainpenetrating 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.
“Highly penetrative nanocarriers loaded with drugs targeted to resistant cells improve treatment of brain tumors
Speaker:
Professor W. Mark Saltzman
Department of Biomedical Engineering
School of Engineering & Applied Science, Yale University
Seminar Date:
Friday, January 20, 2012 - 12:00pm
Location:
BECTON SEMINAR ROOM
Prospect Street
New Haven, CT
Host:
Paul Fleury
Seminar Announcement Brochure: