Development of a Novel Multifunctionally-Graded System for Controlled Drug Delivery and Size Effect on Aptamer Based Fe3O4@Au Core-Shell Nanoparticles

• Main Authors: Chu, Chih-Yuan, 朱志元
• Other Authors: Ko, Fu-Hsiang
• Format: Others
• Language: en_US
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/634925

碩士 === 國立交通大學 === 材料科學與工程學系奈米科技碩博士班 === 104 === Recently, due to the high mortality caused by cancer, development of carriers for cancer therapy had engaged a lot of attentions for many researchers. Among these investigations, superparamagnetic iron oxide nanoparticles (SPIONs) and their derivatives have been widely investigated in numerous medical applications. In this study, we have successfully synthesized superparamagnetic iron oxide nanoparticles by co-precipitation method, and then gold nanoshell was coated by reduction method. This Fe3O4@Au core-shell structure served as a substrate for further applications in multifunctional drug delivery system with both magnetic properties derived from Fe3O4 and optical properties derived from gold nanoshell surface. Because of the specific surface characteristic of gold nanoshell, we could modify special-designed sequence of DNA with thiol bonding. By means of the sequence including not only an aptamer which had been demonstrated with specific binding ability, but also CG-rich fragments which carried doxorubicin (DOX) as anticancer drug, both the drug loading and specific targeting could be achieved . By triggered with high frequency magnetic field (HFMF), high release percentage could be achieved efficiently in relatively short period of time. Besides, by adjusting the concentration of reduction agent, we had synthesized Fe3O4@Au with different size distribution. The thickness of gold nanoshell would influence of Fe3O4@Au in magnetic, surface area and other physical properties, which also affected the performance for cancer therapy. First, temperature increment caused by high frequency magnetic field would decrease with the increasing thickness of nanoshell due to the shield effects. Next, larger surface area, which leads to higher DNA binding concentration, relatively carry more DOX molecules. This phenomenon further results in the difference of chemotherapeutic ability. At last, cytotoxicity of our dsDNA-conjugated Fe3O4@Au drug carrier was investigated under concern for future applications. No obvious apoptosis by in vitro cell viability test exhibited good biocompatibility of our carriers. At the same time, our drug-capsulated carriers had been proved to eliminate cancer cell under HFMF. With both effects of chemotherapy and hyperthermia, lower minimum amount of drug that has to be used was predicted, which means side effects could be reduced effectively. In conclusion, we have successfully built a release- controlled drug delivery system based on a special-designed drug carrier under HFMF treatment, in which chemotherapy, hyperthermia and specific targeting were all integrated.. Moreover, the study of size effect demonstrated that sizes of these particles act as a controllable and efficient factor for drug delivery behavior and the system tend to be more completed consequently.