INVESTIGATION OF BIFUNCTIONAL AGENT POTENTIAL OF TUMOR TARGETED SILICA NANOPARTICLES
Project no. 203 · Status: Kapanmış · 2016
Summary
Pancreatic cancer is the most difficult to diagnose and treatment among cancer types. In addition, survival rate after diagnosis is very low. In recent years, it has been seen that alone conventional treatment methods have not been effective. Instead of that, the application of combined treatment methods has increased. Also, using of nanotechnology in the medical field, the development of teranostic agents that enable both diagnosis and treatment has gained pace. In this thesis, mesoporous silica nanoparticles loaded with Zn phthalocyanine (ZnPc) and targeted with cetuximab antibody (MSNP5) were prepared and labeled with 131I radionuclide. It was determined with the characterization that the encapsulation of Zn phthalocyanine and the surface modification were successfully carried out. At the same time, the hydrodynamic diameter of MSNP5 nanoparticles was determined to be 185.6±22.6 nm. The singlet oxygen (1O2) quantum yield (??) value of ZnPc was found to be 0.60 in toluene. In vitro PDT studies were performed to determine the dark and phototoxicity of ZnPc and nanoparticles by using pancreatic cancer cells (MIA PaCa-2, AsPC-1 and PANC-1). According to the results, MSNP5 nanoparticles showed quite high phototoxic effect, more pronounced than MSNP4 nanoparticles. It was observed from the intracellular uptake studies determined by Fluorometric methods that MSNP5 nanoparticles’ uptake potential was higher than MSNP4 nanoparticles. The radiolabeling efficiency of MSNP5 nanoparticles was found to be quite high (95.5±1.2%) in optimum conditions (pH 9 and 60 minutes reaction time). In addition to this, the highest intracellular uptake yields of 131I-MSNP5 in MIA PaCa-2, AsPC-1 and PANC-1cells were determined as 43.9±3.8%, %41.8±0.2 and %37.9±1.3, respectively at 24 hours incubation time. In conclusion, MSNP5 nanoparticles with targerting cetuximab antibody appear as suitable a theranostic agent for nuclear imaging/therapy and photodynamic therapy of pancreatic tumors.