ANTİKOR TAŞIYAN NANOPARTİKÜLLER KULLANARAK HİPERTERMİ İLE TÜMÖR DOKUSUNUN TEDAVİSİ
Özet
The number of deaths due to cancer has been increasing so this disease has become one of the most important diseases of mankind. Despite the advances in cancer treatment, there isn't 100 % treatment for this disease and there are many side effects of current treatment methods. For these reasons, researchers are exploring ways to improve existing treatment methods and find new methods. One of the alternative methods used in cancer therapy is hyperthermia treatment. Different energy sources and different nanoparticles are used for hyperthermia technique.
In the presented thesis, cancer therapy is investigated with the help of radiofrequency (RF) hyperthermia. Magnetite nanoparticles are used to provide RF hyperthermia. In the other words, the aim of this thesis is to design intelligent inorganic nanoparticles and destroy cancerous cells using RF hyperthermia. For this purpose, firstly magnetite nanoparticles were synthesized by co-precipitation method (10-15 nm). These superparamagnetic nanoparticles were covered with gold ions without losing their magnetic properties. The size of the gold coated magnetite nanoparticles was around 20-30 nm, so the thickness of the gold coating was about 5-10 nm. Magnetic and gold coated magnetic nanoparticles were characterized with Zetapals, FTIR, TEM and VSM.
In another step of the thesis work, the surface modification of the gold-coated magnetic nanoparticles was performed. The cysteamine (2-Aminoethanethiol) molecule was used to create a self-assembled monolayers (SAMs). After that monoclonal antibody (MONOCLONAL ANTI-N CAM Clone NCAM-OB11) was immobilized by the EDC / NHS method. The average size of cysteamine functionalized-gold-coated magnetic nanoparticles was between 25 and 35 nm.
Then the antenna RF system (144.015 MHz) was contrived for RF hyperthermia. Antibody-nanoparticle binding rate and cytotoxicity test were performed and after that in-vitro and in-vivo experiments were done.
In in-vitro studies, a concentration of 20 μg/ml nanoparticle was used according to the results obtained from the antibody-nanoparticle binding rate and the MTT assay. In MCF-7 cells, 58.7 % apoptosis and 14.88 % necrosis were observed in the radiofrequency hyperthermia (144.015 MHz, 120 W, 50 min).
Animal experiments were done after the in-vitro step. For this step, tumor were formed in nude mice. Then the antibody immobilized/gold-coated magnetic nanoparticles were injected into the mice in 2 different ways (Intra-tumor and Intra-venous) and MRI image was taken. RF hyperthermia (144.015 MHz, 120 W, 50 min) was applied in continuation of the research. At the end of the third week after this phase, approximately 34% decreased in the tumor sizes of the intravenously treated mice groups and 53% reduced in the tumor sizes of the intravenously cured mice groups.
