Date(s) - 11/17/2014
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.
W. Mark Saltzman is an engineer and educator. Dr. Saltzman’s research in the fields of drug delivery, biomaterials, nanobiotechnology, and tissue engineering is described in over 250 research papers and 15 patents. He is the author of three textbooks: Biomedical Engineering (2009), Tissue Engineering (2004), and Drug Delivery (2001).
The grandson of Iowa farmers, Mark Saltzman earned degrees in chemical engineering (B.S. Iowa State University 1981 and M.S. MIT 1984) and medical engineering (Ph.D. MIT 1987). He served on the faculty at Johns Hopkins (1987-1996), Cornell (1996-2002), where he was the first BP Amoco/H. Laurance Fuller Chair, and Yale, where he has been the Goizueta Foundation Professor since 2002. He became the founding chair of the Yale’s Department of Biomedical Engineering in 2003.
Dr. Saltzman has been recognized for his excellence in research and teaching. He received the Mines Medal (2014); the Camille and Henry Dreyfus Foundation Teacher-Scholar Award (1990); the Allan C. Davis Medal (1995); the Controlled Release Society Young Investigator Award (1996); and the Professional Progress in Engineering Award from Iowa State University (2000). He has been elected a Fellow of the National Academy of Inventors (2014); Fellow of the American Institute for Medical and Biological Engineering (1997); a Fellow of the Biomedical Engineering Society (2010); and a Member of the Connecticut Academy of Science & Engineering (2012). He has delivered over 200 invited lectures including the Britton Chance Distinguished Lecture at the University of Pennsylvania (2000) and the Distinguished Lecture of the Biomedical Engineering Society (2004).
Dr. Saltzman has taught dozens of college courses including Heat & Mass Transfer, Material & Energy Balances, Engineering of Drug Delivery, Physiological Systems, and Molecular Transport & Intervention in the Brain. His course Frontiers of Biomedical Engineering is available to everyone through Open Yale Courses (http://oyc.yale.edu).