TY - JOUR
T1 - Curcumin loaded dendrimers specifically reduce viability of glioblastoma cell lines
AU - Gallien, John
AU - Srinageshwar, Bhairavi
AU - Gallo, Kellie
AU - Holtgrefe, Gretchen
AU - Koneru, Sindhuja
AU - Otero, Paulina Sequeiros
AU - Bueno, Catalina Alvarez
AU - Mosher, Jamie
AU - Roh, Alison
AU - Kohtz, D. Stave
AU - Swanson, Douglas
AU - Sharma, Ajit
AU - Dunbar, Gary
AU - Rossignol, Julien
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/10/1
Y1 - 2021/10/1
N2 - 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 viabil-ity, 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 effec-tive, 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 provid-ing a promising new route for delivering cancer therapeutics. Our results with curcumin suggest that antioxidants are good candidates for treating glioblastoma.
AB - 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 viabil-ity, 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 effec-tive, 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 provid-ing a promising new route for delivering cancer therapeutics. Our results with curcumin suggest that antioxidants are good candidates for treating glioblastoma.
KW - Cancer
KW - Curcumin
KW - Glioblastoma
KW - Nano-molecule
KW - PAMAM dendrimers
KW - Therapy
KW - Toxicology
UR - http://www.scopus.com/inward/record.url?scp=85116987239&partnerID=8YFLogxK
U2 - 10.3390/molecules26196050
DO - 10.3390/molecules26196050
M3 - Article
C2 - 34641594
AN - SCOPUS:85116987239
VL - 26
JO - Molecules
JF - Molecules
SN - 1420-3049
IS - 19
M1 - 6050
ER -