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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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