| Autor: |
Jiangbing Zhou, Patel, Toral R., Sirianni, Rachael W., Strohbehn, Garth, Ming-Qiang Zheng, Nha Duong, Schafbauer, Thomas, Huttner, Anita J., Yiyun Huang, Carson, Richard E., Ying Zhang, Sullivan Jr., David J., Piepmeier, Joseph M., Saltzman, W. Mark |
| Předmět: |
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| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 7/16/2013, Vol. 110 Issue 29, p11751-11756, 6p |
| Abstrakt: |
Current therapy for glioblastoma multiforme 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: (i) brain-penetrating polymeric nanoparticles that can be loaded with drugs and are optimized for intracranial convection-enhanced delivery and (ii) 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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