Tumor Theranostic Applications Of Two Small Molecule Drugs And SERS Technology Of Targeted Nanogold

People have been always focused on how to find the low-toxic,convenient and targeted drugs which used in the theranostic of tumors.Therefore,this dissertation mainly studied the therapeutic effects of natural Kamabakurin and ponatinib derivative PA on chronic myelogenous leuke mia and synthesized the targeted nanogold materials for cancer research.The main experiment contents include the following three parts:（1）The three chronic myelogenous leukemia cells were studied by using the natural Kamabakurin.The experimental results showed that at 6μg/mL Kamebakaurin could effectively inhibit cell proliferation,affect the cell apoptosis through reducing mitochondrial membrane potential and increase reactive oxygen species.Western-blotting and immunohistochemistry revealed that Kamebakaurin could inhibit the expression of Bcr-Abl and its phosphorylation.Animal experiments illustrated that Kamebakaurin significantly refrained the growth of tumor,without obvious toxicity to the five organs,which could be seen from H-E staining.（2）The ponatinib derivative of PA was synthesized by theoretical simulated calculation.The related biological experiments were performed with three cells（K562,KBM5 KBM5-T315I）,the IC₅₀ values of the three cells were 2.45nM,3.26nM and 6.97nM,respectively.At 8nM,PA obviously induced apoptosis and restrained the expression of the fusion gene Bcr-Abl,including its phosphorylation.Histopathological analysis and TUN EL staining showed that there were no effects on the five viscera,especially for the liver.（3）The gold nanoparticles were uniform and the size was about 20nm.Then the gold nanoparticles were modified using 4-MBA,SH-PEG and epidermal growth factor receptor.Meanwhile,we studied different concentration of modified groups.The raman signal of functionalized gold nanoparticles were detected and successfully applied to cell dark field imaging.