Date of Award
Winter 12-14-2018
Document Type
Thesis
Degree Name
Master of Science in Chemistry (MSChem)
Department
Chemistry
First Advisor
Dr. Santimukul Santra
Second Advisor
Dr. Tuhina Banerjee
Third Advisor
Dr. Irene Zegar
Fourth Advisor
Dr. Phillip Harries
Abstract
Men are most susceptible to prostate cancer in the United States. The general treatment options include surgery, hormone therapy, chemotherapy, and radiation therapy. But in recent days, the nanoformulation have shown promising applications in overcoming the drawbacks of the currently available treatment options. To complement, we tried to enhance the capability of the nanoparticle formulation by loading them with a novel drug combination for the treatment of prostate cancer. Herein, we synthesized folate conjugated iron oxide nanoparticles encapsulated with doxorubicin and olaparib for imaging and targeted treatment of prostate cancer. Both drugs are approved by FDA for clinical cancer treatment. IONPs coated with polyacrylic acid will be synthesized with water-based precipitation method, followed by functionalization with folate using “click” chemistry. Briefly, the IONPs will be first propargylated using EDC/NHS carbodiimide chemistry followed by CuI catalyzed “click” chemistry using azide-functionalized folic acid. Next, doxorubicin and olaparib will be co-encapsulated in the IONPs using the solvent diffusion method. The resulting therapeutic nanomedicines will be characterized by measuring size, zeta potential, and UV/fluorescence emission and absorbance. The two drugs are being used together to explore if the synergistic effect they normally have will still be in effect while they are encapsulated in nanoparticles. The cytotoxicity will be explored through MTT assay, and cell uptake studies. The nature of the cell death will be observed through apoptosis, ROS, and comet assay studies. Finally, the antimetastatic potential of the therapeutic nanoparticles will be studied via migration assay and reported.
Recommended Citation
Ansare, Momin, "Combination Therapy: PARP Inhibitor Synergizes the Therapeutic Efficacy of Doxorubicin in the treatment of Prostate Cancer" (2018). Electronic Theses & Dissertations. 269.
https://digitalcommons.pittstate.edu/etd/269
