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Curcumin Loaded Dendrimers Specifically Reduce Viability of Glioblastoma Cell Lines
Authors:John Gallien  Bhairavi Srinageshwar  Kellie Gallo  Gretchen Holtgrefe  Sindhuja Koneru  Paulina Sequeiros Otero  Catalina Alvarez Bueno  Jamie Mosher  Alison Roh  D. Stave Kohtz  Douglas Swanson  Ajit Sharma  Gary Dunbar  Julien Rossignol
Abstract:Glioblastoma (GB) is a deadly and aggressive cancer of the CNS. Even with extensive resection and chemoradiotherapy, patient survival is still only 15 months. To maintain growth and proliferation, cancer cells require a high oxidative state. Curcumin, a well-known anti-inflammatory antioxidant, is a potential candidate for treatment of GB. To facilitate efficient delivery of therapeutic doses of curcumin into cells, we encapsulated the drug in surface-modified polyamidoamine (PAMAM) dendrimers. We studied the in vitro effectiveness of a traditional PAMAM dendrimer (100% amine surface, G4 NH2), surface-modified dendrimer (10% amine and 90% hydroxyl-G4 90/10-Cys), and curcumin (Cur)-encapsulated dendrimer (G4 90/10-Cys-Cur) on three species of glioblastoma cell lines: mouse-GL261, rat-F98, and human-U87. Using an MTT assay for cell viability, we found that G4 90/10-Cys-Cur reduced viability of all three glioblastoma cell lines compared to non-cancerous control cells. Under similar conditions, unencapsulated curcumin was not effective, while the non-modified dendrimer (G4 NH2) caused significant death of both cancerous and normal cells. By harnessing and optimizing the components of PAMAM dendrimers, we are providing a promising new route for delivering cancer therapeutics. Our results with curcumin suggest that antioxidants are good candidates for treating glioblastoma.
Keywords:PAMAM dendrimers   curcumin   toxicology   nano-molecule   therapy   glioblastoma   cancer
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