Çoklu İlaca Dirençli Kanser Hücre Hattına Nanopartiküllerle İlaç Aktarımı

Abstract

Nanotechnology and Nanomedicine applications are interdisciplinary sciences that began to take the place of traditional treatments increasingly widespread. As is known, chemotherapy, radiotherapy and / or surgical methods extremely reduce the success and effectiveness of the treatment of many diseases like cancer. Classical chemotherapy drugs are incapable of reaching the desired site in the body, also they can not achieve to therapeutic doses in cancer cells. So novel studies is focused on cancer diagnostic and treatment utilizing biocompatible carrier (of nanoparticles) which are important study fields of nanotechnology. In this thesis, loading of a cancer drug (doxorubicin) into polymeric nanoparticles and determination of its releasing studies, treating the drug-resistant Small Cell Lung Cancer Cells (SCLC) and Non-Small Cell Lung Cancer Cells (NSCLC) (H69AR and H1299) with these nanoparticles and evaluation the apoptotic cell rate, cell proliferation and cytotoxicity and finally comparative apoptosis, proliferation and toxicity studies of the drug-loaded particles in the presence of quercetin (a bioflavonoid) were aimed. Moreover, it was intended to direct the cells to apoptosis reducing the resistance of the drug resistant Small Cell Lung Cancer Cells via quercetin and releasing the drug at effective dose to cells via nanoparticles. For this purpose, in the first part of the study, synthesis and characterization of chitosan nanoparticles and the drug release studies were performed. Firstly dissolution of the low molecular weight chitosan polymer in a weak acetic acid was achieved, and then interaction of chitosan with tripolyphosphate (TPP) which is a crosslinker was carried out adjusting the appropriate pH of chitosan solution, and finally chitosan nanoparticles were obtained. For purpose of determining of physicochemical properties, size distribution, particle surface charge analysis of prepared nanoparticles were evaluated and for determination of morphological properties, AFM (Atomic Force Microscopy) technique was utilized. After optimization has been accomplished, cancer drug doxorubicin was loaded into the resulted nanoparticles for in vitro release profile and the graphic of time-dependent controlled release was obtained. In the second part of the study, prepared drug loaded nanoparticles with quercetin were interacted with cells then the cytotoxicity and the proliferation rates were assessed comparatively. For morphological evaluation of dying cells, the apoptotic-necrotic index of cells have been obtained using the double staining method. And the time-dependent changes in cell proliferation in the RTCA (Real-Time Cell Analyzer) system have been analysed. Obtained results show that drug loaded nanoparticles with quercetin is a possible chemotherapeutic option for cancer therapy.