Date of Award
Spring 5-11-2018
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Chemistry
First Advisor
Dr. Santimukul Santra, ssantra@pittstate.edu
Second Advisor
Dr. Dilip. K. Paul, dpaul@pittstate.edu
Third Advisor
Dr. Irene Zegar, izegar@pittstate.edu
Fourth Advisor
Dr. Jian Hong, jhong@pittstate.edu
Abstract
Prostate cancer is the most common amongst men. According to ACS 2018 statistics, about 164,690 new cases appear and 29,430 deaths occur. Nearly 6 in 10 cases are diagnosed in men over 50 years of age and often there are no early symptoms. The treatment options include surgery, chemotherapy, hormonal therapy and/or radiation and it can often be treated successfully. However, the poor management and adverse effects demanded ways to find better treatment option. Towards the development of a personalized medicine for prostate cancer treatment, we proposed to design prostate cancer targeting magnetic nanoplatform. This integrates various key components such as combination of drugs, imaging agents, targeting ligands and targeted delivery of these cargos in high concentrations to tumor. A triple drug regimen of Oxaliplatin, Irinotecan and 5-Fluorouracil was used, which was already known to be effective in the treatment of colorectal cancer and pancreatic cancer. These three drugs were encapsulated in folate conjugated magnetic nanoparticles and tremendous effect of cell death via oxidative stress in LNCaP cells was observed. The synthesis of magnetic nanoparticles, surface conjugation with folic acid using “Click” chemistry, encapsulations of cargos and their characterization were discussed in detail. Having folate conjugated magnetic nanomedicine, the drug delivery was targeted to prostate cancer and had no to minimal toxic effects on the healthy cells. Individual mechanism of the drugs and their synergistic effect in the treatment was evaluated by performing optical microscopy, magnetic resonance imaging experiments as well as cell-based assays such as ROS, apoptosis and necrosis, cytotoxicity, migration, and comet. This study showed us the targeted nanoformulation which we designed was successful in exhibiting the toxic effects on a tumor cell.
Recommended Citation
Tummala, Tanuja, "Targeted Triple Drug Regimen for the Treatment of Prostate Cancer" (2018). Electronic Theses & Dissertations. 253.
https://digitalcommons.pittstate.edu/etd/253
