具診斷光熱性奈米微胞載體藉雷射促使藥物釋放達光熱及化學治療

Laser Triggered Release of Doxorubicin Induced Photothermal-Chemotherapy via Theranostic Micelle

陳婉宜(Yuan-I Chen)

指導教授 ： 謝銘鈞

國立臺灣大學/工學院/醫學工程學研究所/碩士(2014年)

https://doi.org/10.6342/NTU.2014.11269

摘要

有機化合物中的花青染料(Cyanine dye)種類繁多，不同結構及不同種類在不同的領域中，都有其特有的功能，Cyanine dye中的Heptamethylcyanine dye (Cy)已在近幾年的研究中被證實其在近紅外光波段(600-1000nm)可以產生近紅外光影像及光熱治療(Photothermal therapy)的功能，但Cy為一疏水性物質，導致其在臨床的應用上有其限制。為了克服其Cy在臨床應用的缺點且保有顯影及光熱治療的功能，此篇研究利用有機合成的方式，利用Cy與親水性材料mPEG和疏水性材料CL合成一新的高分子聚合物mPEG-Cy-PCL，促使增加Cy在水相溶液中的溶解性，藉由親疏水性質之自我聚集的方式在水相溶液中製備奈米微胞載體Empty@Cy-micelle，此載體保有Cy原先顯影及光熱治療之特性，進而發展一新的多功能藥物傳輸系統。
利用Empty@Cy-micelle所發展的藥物傳輸系統，在疏水的核心包覆疏水性藥物阿黴素(Doxorubicin)，成為一多功能型的奈米藥物Doxo@Cy-micelle。Doxo@Cy-micelle藉由增強通透性與延遲效應(EPR effect)來增加藥物在腫瘤的累積量，利用載體本身具有即時性的影像導引來觀察其在不同的器官及腫瘤中的累積分佈量，於特定之腫瘤區域進行光熱治療時溫度的變化，來增加藥物在腫瘤區域的釋放量，進而達到控制藥物釋放的效果，並同時產生光熱治療和化學治療。在物理性質方面，粒徑大小約為120-130nm，化療藥物的包覆率也可達六成以上，另外，在細胞及動物實驗中，可以發現，結合光熱治療及化學治療對於腫瘤的毒殺能力，較分別的單一治療有著較佳的治療效果並具有協同效應(Synergistic effect)，因此，藉由發展一多功能性的奈米藥物載體，期許在未來不同的癌症中有更多方面運用。

關鍵字

奈米微胞載體 ； 近紅外光影像 ； 化學治療 ； 控制藥物釋放 ； 協同作用

並列摘要

Heptamethylcyanine dyes (Cy) are capable of providing dual functions in near-infrared (600-1000nm) imaging and Photothermal therapy (PTT). Its characteristic, insolubility, may result in the limitation of clinic application. In order to overcome the disadvantage of Cy and preserve its functions, the new polymer, mPEG-Cy-PCL, was synthesized to increase solubility. By using mPEG-Cy-PCL, self-assembled theranostic micelles (Empty@Cy-micelle) were developed to reach the effect of PTT.
Empty@Cy-micelles were loaded with doxorubicin (Doxo@Cy-micelle) and used Enhanced Permeability and Retention (EPR) effect to accumulate in tumor. Therefore, Doxo@Cy-micelles not only allowed image-guided drug delivery but also real-time monitoring of the drug in the tumor. Moreover, Doxo@Cy-micelles showed temperature increase by laser at specific region facilitating faster and more doxo relase and reached a combination of photothermal-chemotherapy. Regarding to the physical and chemical properties, its sizes was about 120-130 nm and the drug encapsulated efficiency would more than 60 %. In addition, the experiment of in vitro and in vivo indicating that photothermal-chemotherapy had more treatment efficacy and synergistic effect than photothermal therapy or chemotherapy alone. Overall, the multifunctional nanotheranostic platform based on mPEG-Cy-PCL would hopefully be applied in various cancaer treatment in the future.

並列關鍵字

micelle ； near-infrared (NIR) imaging ； photothermal therapy (PTT) ； chemotherapy ； control drug release ； synergistical effect

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