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.

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