Preparation of chemotheraputic agent and suitable siRNA-loaded polymeric nanoparticles to be used in breast cancer treatment and determination of their effects

The incidence of cancer is increasing day by day. Breast cancer is the most common type of cancer in women all over the world. Chemotherapy agents used in cancer treatments are insufficient if the tumor becomes resistant. For this reason, the development of innovative and more effective therapeutic agents in cancer therapies has accelerated, and complex therapies in which different agents are used together have come to the fore. In breast cancer treatments, drug resistance often develops and therefore the possibility of metastasis is high. In the presented thesis studies, silencing of the gene causing drug resistance in breast cancer was targeted by using RNAi-based gene silencing strategies, and a special carrier system was designed for the transport of genetic material and anticancer drugs. Within the scope of the thesis, the expression of the MDR1 gene, which causes drug resistance, was tried to be suppressed, in this context, siRNA-loaded dextran-coated biocompatible iron-oxide magnetic nanoparticle carriers targeting the MDR1 gene were prepared. Necessary experiments were carried out for the optimization of these carriers and characterization studies were carried out using Doxorubicin loaded dextran-coated iron nanoparticles FTIR, SEM, DLS, and EDX.MTT and mRNA analyzes were performed to evaluate the suppression of P-gp expression in MCF-7 cells by iron nanoparticles produced as doxorubicin and MDR1-siRNA carriers. As a result, doxorubicin and MDR-1 siRNA were successfully loaded on dextran-coated iron oxide nanoparticles and the efficiency of the nanoparticle developed in the MCF-7 cell line was evaluated.