One-step Synthesis of Irregular Shaped Gold Nanoparticles Modified with AS1411 for the Inhibition of Cancer Cell Growth

• Main Authors: Chiu, Shih-Jen, 邱詩任
• Other Authors: Huang, Chih-Ching
• Format: Others
• Language: zh-TW
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/02490312591110911951

碩士 === 國立臺灣海洋大學 === 生命科學暨生物科技學系 === 105 === AS1411 is a guanine-rich (G-rich) oligodeoxyribonucleotide aptamer, which can form a stable G-quadruplex structure. Studies show that AS1411 can specifically bind to nucleolin (NCL), a multifunctional nucleolar protein located in cell. NCL is overexpressed on cell membrane in most cancer cells. Hence, AS1411-conjugated nanoparticles can be internalized in to the cells via receptor-mediated endocytosis after they specifically interact with nucleolin on the cell membrane, that enables cancer cell labeling and inhibition of cell growth. In this study, we developed a simple one-step method for the synthesis of irregular shaped gold nanoparticles (Au NPs) modified with poly (adenine) -terminal AS1411. The functional Au NPs are prepared through a simple reaction of HAuCl4 with Good's buffers such as (4-(2-Hydroxyethyl)-1-piperazineethanesulfonic acid, HEPES), (3-(N-morpholino) propanesulfonic acid, MOPS), (3-(N-morpholinyl)-2-hydroxypropanesulfonic acid, MOPSO) and (piperazine-1,4-bis(2-hydroxy-3-propanesulfonic acid, POPSO) in presence of AS1411. The AS1411 aptamers self-assemble on Au NPs via strong interaction between poly (adenine) and Au NPs. The concentration of AS1411 plays a vital role in controlling the morphology and size of Au NPs. The preliminary results show that AS1411−Au NPs can selectively target MCF-7 breast cancer cells. We believe that, after the AS1411−Au NPs are internalized in to the cells, the intracellular glutathione will induce the AS1411 release from Au NPs, and therfore, they inhibit cancer cell growth. Our results reveal that glutathione can induce the release of about 39% of AS1411 from spherical Au NPs (13 nm). However, AS1411−Au NPs do not show enhanced inhibition effect on cancer cell growth compared to free AS1411. In our future work we will employ AS1411–Au NPs as a cancer drug carrier to specifically target cancer cells and enhance their inhibition properties.