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To address these challenges, we combined two major advances in technology: (\n                    <jats:italic>i<\/jats:italic>\n                    ) brain-penetrating polymeric nanoparticles that can be loaded with drugs and are optimized for intracranial convection-enhanced delivery and (\n                    <jats:italic>ii<\/jats:italic>\n                    ) repurposed compounds, previously used in Food and Drug Administration-approved products, which were identified through library screening to target BCSCs. Using fluorescence imaging and positron emission tomography, we demonstrate that brain-penetrating nanoparticles can be delivered to large intracranial volumes in both rats and pigs. We identified several agents (from Food and Drug Administration-approved products) that potently inhibit proliferation and self-renewal of BCSCs. When loaded into brain-penetrating nanoparticles and administered by convection-enhanced delivery, one of these agents, dithiazanine iodide, significantly increased survival in rats bearing BCSC-derived xenografts. This unique approach to controlled delivery in the brain should have a significant impact on treatment of glioblastoma multiforme and suggests previously undescribed routes for drug and gene delivery to treat other diseases of the central nervous system.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1304504110","type":"journal-article","created":{"date-parts":[[2013,7,2]],"date-time":"2013-07-02T00:42:22Z","timestamp":1372725742000},"page":"11751-11756","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":253,"title":["Highly penetrative, drug-loaded nanocarriers improve treatment of glioblastoma"],"prefix":"10.1073","volume":"110","author":[{"given":"Jiangbing","family":"Zhou","sequence":"first","affiliation":[{"name":"Departments of aBiomedical Engineering,"},{"name":"Neurosurgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toral R.","family":"Patel","sequence":"additional","affiliation":[{"name":"Neurosurgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael W.","family":"Sirianni","sequence":"additional","affiliation":[{"name":"Diagnostic Radiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garth","family":"Strohbehn","sequence":"additional","affiliation":[{"name":"Departments of aBiomedical Engineering,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Qiang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Diagnostic Radiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nha","family":"Duong","sequence":"additional","affiliation":[{"name":"Departments of aBiomedical Engineering,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Schafbauer","sequence":"additional","affiliation":[{"name":"Diagnostic Radiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita J.","family":"Huttner","sequence":"additional","affiliation":[{"name":"Pathology, Yale University, New Haven, CT 06511; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyun","family":"Huang","sequence":"additional","affiliation":[{"name":"Diagnostic Radiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard E.","family":"Carson","sequence":"additional","affiliation":[{"name":"Departments of aBiomedical Engineering,"},{"name":"Diagnostic Radiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[{"name":"W. 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