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

pH-Responsive Drug Release from Gold Nanorods by NIR irradiation for Targeted Drug Delivery

陳玠瑋(Chieh-Wei Chen)

指導教授 ： 黃郁棻

國立清華大學/原子科學院/生醫工程與環境科學系/碩士(2012年)

https://doi.org/10.6843/NTHU.2012.00418

摘要

激活性奈米材料泛指材料在受到外力刺激時，會產生物理或化學現象的改變，例如產生熱、光、化學反應、和體積及運動模式改變等，近年來在生醫領域備受矚目。本研究利用連續波型的808 nm雷射照射金奈米棒 （Au NRs），使Au NRs吸收雷射能量轉換而成的熱能，能加速其表面具有酸鹼應答特性之藥物–PDPH-Dox釋放行為，提高藥物治療果效。為減少藥物在傳遞過程因生理酸鹼值（pH 7.4）導致藥物滲漏產生之毒性，Dox以共價性鍵結修飾於Au NRs上。然而在酸性環境下（pH 4.5~5.5）藥物Dox和載體（Au NRs）之間的腙鍵結 （Hydrazone bond）會被酸解而從載體上釋放出藥物。為增進載體對於目標細胞（CCRF-CEM）的特異性標定，同時在Au NRs表面組裝眾多對於有強親和力的適體–Sgc8c。此外，因巨噬細胞可於腫瘤區域累積，為增進奈米藥物對於腫瘤的傳遞效率，將Sgc8c替換為玻尿酸的奈米藥物載體，可與巨噬細胞（RAW 264.7）表面的CD44藉由特異性標定累積於細胞內，形成一細胞型載體。研究結果顯示，本研究成功開發一兼具酸鹼值和近紅外光應答特性之新型奈米藥物載體，透過雷射光照射，可精準控制奈米載體在細胞內的釋藥行為，藉此雙重釋藥機制可結合藥物及光熱治療，提升毒殺癌細胞效率。同時利用細胞型載體以共培養方式，照射NIR雷射毒殺另一癌細胞Tramp-C1。

關鍵字

金奈米棒 ； 藥物傳遞 ； 光熱轉換效應

並列摘要

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.

並列關鍵字

Gold nanorod ； Drug delivery ； Photothermal effect

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