Akademik Veri Yönetim Sistemi
Tezin Türü: Doktora
Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Fen Bilimleri Enstitüsü, Fen Bilimleri Enstitüsü, Türkiye
Tezin Onay Tarihi: 2013
Öğrenci: GÖZDE ÜNSOY
Danışman: UFUK GÜNDÜZ
Özet:Chitosan superparamagnetic nanoparticles, loaded with Doxorubicin and Bortezomib were synthesized for treatment of breast and cervical cancers by targeted drug delivery. In vitro cytotoxicity analyses revealed that the efficacy of drugs was highly increased when applied as loaded on nanoparticles. Chitosan superparamagnetic iron oxide nanoparticles (CSMNPs) were in-situ synthesized at different sizes by ionic crosslinking method. The characterization of nanoparticles was performed by XRD, XPS/ESCA, FTIR, TEM, DLS, TGA, VSM and zeta potential analyses. The XRD and XPS analyses proved that synthesized iron-oxide was magnetite (Fe3O4). Chitosan coating on the surface of magnetite was confirmed by FTIR. Average core size of CSMNPs were between 2-8 nm in TEM and hydrodynamic diameters were between 58-103 nm in DLS. TEM results demonstrated a spherical morphology. TGA results indicated that chitosan content of CSMNPs were between 15-23%. CSMNPs were found superparamagnetic by VSM analyses. The cellular uptake of nanoparticles was visualized by fluorescence microscopy and cytotoxicity was determined by XTT analyses on MCF-7, MCF-7/Dox, SiHa and HeLa cell lines. Doxorubicin and Bortezomib loading, release and stability efficiencies of CSMNPs were analyzed by considering the different parameters. CSMNPs are not cytotoxic without the drug load. When these drugs are loaded on CSMNPs, the antiproliferative efficiencies of drugs increases and resistance to these drugs is eliminated. IC50 values of drugs remarkably decreases when the drugs are given to the cells as loaded on CSMNPs. Proapoptotic Puma and Noxa genes were up regulated while antiapoptotic Bcl-2, Survivin and cIAP-2 genes were down regulated in drug loaded CSMNP treated cells. Consequently, CSMNPs synthesized at various sizes would be effectively used for the pH dependent release of Doxorubicin and Bortezomib. Results of this study can provide new insights in the development of pH responsive magnetic targeted drug delivery systems to overcome the side effects and resistance problem of conventional chemotherapy.