TY - BOOK AU - Hosseini,Rouminasadat AU - Erdengiz,Deran TI - THE EFFECT OF COMBINATORIAL THERAPEUTICS ON BREAST CANCER CELLS USING NANOPARTICLE DRUG DELIVERY SYSTEM PY - 2022/// KW - Breast KW - Dissertations, Academic KW - Cancer KW - Drug delivery systems KW - Metformin KW - Nanoparticles N1 - Thesis (MSc) - Cyprus International University. Institute of Graduate Studies and Research Bioengineering Department; Includes bibliography (sheets 47-55) N2 - ABSTRACT Breast cancer is one of the most common types of cancer with an estimated incidence rate of 2.26 million in 2020 and ranked number one as leading cause of cancer mortality in women. So far it has been treated and controlled by conventional therapies such as chemotherapy, radiation therapy and surgery. Since 2010, nanoparticle drug delivery systems have demonstrated great potential in the treatment of cancers. When compared to conventional therapeutics, the advantages of nanoparticles include lower side effects, higher biocompatibility, and greater stability, enhanced targeting, and lower toxicity. So far various types of nanoparticles, such as albumin, iron oxide, gold and silver nanoparticles have shown great potential in cancer treatment and drug delivery; furthermore, recent studies have shown that ZnO nanoparticles (NPs) have cytotoxic effect on cancer cells and can induce apoptosis by generating cellular oxidative stress. In addition, researchers are using drug-repurposing methods to further the development of cancer therapeutics. Experimental data have shown that metformin, which is originally a type-2 diabetes treatment drug, also has anticancer potentials and can reduce the proliferation of cancer cells. We hypothesized that combinatorial exposure of ZnO and metformin-encapsulated carboxymethyl chitosan (MeCMC) NPs will generate enhanced cytotoxicity and apoptosis, as well as reduced proliferation in breast cancer cells, compared to single exposure of either one over time. To answer our hypothesis, we used MDA-MB-231, triple negative breast cancer cell lines, to assess the differences between combinatorial exposure of ZnO and MeCMC NPs and their effect alone. The results obtained from the experiment did not show a significant difference in the cell viability between single and double exposure when comparing the same concentration of both CMC NP and metformin, however, it showed a significant decrease of cell viability by comparing the same dose of the drug in different concentrations of CMC NP between single and double exposure. In addition, our results indicate that even though combinatorial exposure did not show a significant change in viability, it may have a significant effect on cell proliferation. Keywords: Breast cancer, Carboxymethyl Chitosan, Combinatorial Therapeutics, Drug Delivery, Drug Repurposing, Metformin, Nanoparticle, Zinc Oxide ER -