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金奈米棒於酸鹼及光熱應答型藥物載體設計及其於癌症標靶治療之應用
Thesis

金奈米棒於酸鹼及光熱應答型藥物載體設計及其於癌症標靶治療之應用

陳玠瑋
Masters, 國立清華大學, 生醫工程與環境科學系
2011

Abstract

金奈米棒 藥物傳遞 光熱轉換效應 Gold nanorod Drug delivery Photothermal effect
In this study, a doxorubicin (Dox) conjugated gold nanorod (Dox-Au NR) which exhibits a pH-responsive drug release profile has been constructed successfully. The antitumor drug Dox was covalently linked to Au NRs to reduce the overall toxicity of the drug in physiological conditions. However, the acid-labile hydrazone linker, connecting the Dox-Au NR conjugates could be cleaved in an acidic environment. Furthermore, multiple aptamers, sgc8c have also been assembled on the NR surface, providing strong binding affinity with targeted cancer cells through simultaneous multivalent interactions with the cell membrane receptors. Owing to the photothermal effect that Au NR could convert the absorbed light energy to heat, CCRF-CEM cells incubated with Dox-Au NR conjugates were greatly damaged after near-infrared (NIR) light exposure. Our results demonstrated that these novel drug nanocarriers which combine pH- and NIR-responsiveness are highly promising for precise drug releasing in targeted drug delivery. Furthermore, an efficient approach for tumor-targeted drug delivery system was developed with macorphage (RAW 264.7) as the targeting vehicle and a hyaluronic acid conjugated gold nanorod (HA-Au NR) as the drug carrier. This novel strategy provides a great potential to actively deliver nano-therapeutics to tumors utilizing macrophages as tumor-tropic carriers. The synergistic NIR photothermally enhanced drug release of HA/Dox-Au NRs also provides a considerable contribution to enhanced tumor-cell(Tramp-C1) apoptosis and low systematic toxicity.

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