Date of Award

Spring 5-10-2019

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

First Advisor

Dr. Santimukul Santra

Second Advisor

Dr. Dilip Paul

Third Advisor

Dr. Irene Zegar

Fourth Advisor

Dr. Phillip Harries

Abstract

Cancer is known to be a detrimental disease and it accounts for many deaths every year. In women Triple negative breast cancer (TNBC) known to be a very aggressive type of tumor. Current treatment approaches are abortive and have many side effects. With the recent advances in nanotechnology and immunotherapy for cancer treatment, we have designed new nanomedicine that combines both the aspects of cancer treatment. In this work, we have developed an anti-PD-L1-conjugated, Doxo-SS-Gd MR imaging agent encapsulating iron oxide nanoparticles (IONPs) to form IONP-Doxo-SS-Gd-PD-L1 nanomedicine for the targeted MR imaging and treatment of TNBC. The anti-PD-L1 acts as a checkpoint inhibitor in the PD-1 & PD-L1 interaction, helping in generating an immune response against the cancer cells. Furthermore, the Gd-DTPA functionalized doxorubicin prodrug (Doxo-SS-Gd), is known as a chemotherapeutic drug and a strong T1 MR agent, which would provide bright T1 MR contrast for the imaging of tumor. To assess the therapeutic potential of the designed nanomedicine in treating cancer, various cell bases experiments were carried out. The bright and dark MR contrast of the IONP-Doxo-SS-Gd- PD-L1 nanomedicine was also evaluated using clinical MRI instrument (B = 9.3T). Therefore, the developed immunochemotherapeutic-nanomedicine provides combination approaches for the synergistic (immunotherapy and chemotherapy) treatment of TNBC and further has MR imaging functionality for diagnosis and treatment monitoring.

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