開發具聲光顯影與磁控制藥物釋放之標靶藥物奈米載體材料結構

Abstract

癌症腫瘤治療乃為全球醫療研究所最棘手與關注的問題。在傳統的癌症化學治療方法中，抗癌藥物不 能區分正常細胞與癌細胞，因此造成有限的治療效果與許多副作用。在本計畫中，利用材料與藥物的 結合，設計與製備一種具多功能性的藥物奈米載體，除了具有控制釋放藥物與標靶癌細胞之功能，還 可以同步利用聲光顯影，追蹤腫瘤治療情形。然而，傳統的藥物釋放，僅利用藥物載體的特性與所在 的環境變化來運作，在人體中並未真正達到完善地控制釋放的目標。基於此創新的研究構想，提出利 用藥物載體的製程控制，發展具有磁敏感性的奈米核殼膠囊結構，在未加磁場的狀態下，該奈米膠囊 藥物自然釋放量趨近於零，然而當此奈米膠囊抵達腫瘤位置時，可以利用外部的磁場刺激磁奈米載 體，控制藥物快速的局部釋放，將大量的抗癌藥物釋放於腫瘤之位置，達到腫瘤治療的效果。此外， 利用奈米載體表面修飾技術，架接腫瘤標把分子於奈米膠囊的表面上，提升奈米膠囊進入癌細胞的效 率，將載體大量累積於腫瘤位置，並且搭配聲光顯影，來追蹤該奈米膠囊於體內的位置，期望在未來 可達到快速有效率的局部釋藥於腫瘤細胞，並同時於體內偵測藥物釋放情形，達到另一個新世代標靶 治療的需求。

The magnetic nanocapsules capable of carrying therapeutic drug molecules and possessing targeted therapy were synthesized as the bifunctional magnetic vectors that can be triggered for control release of therapeutic agent by an external magnetic field and bioimaging through photoacoustic tomography. The drug release profiles of cpsules can be well-regulated through an ultra thin layer of outer magnetic shell. Remote control of drug release from the nanocapsules was successfully achieved using an external magnetic field where the core phase being structurally disintegrated to a certain extent while subjecting to magnetic stimulus, resulting in a burst release of the encapsulated drug. However, a relatively slow and linear release restored immediately right after removal of the stimulus. More than surprisingly, the nanocapsules demonstrated a high uptake efficiency by HeLa cell line while the surface of the capsules was modified by the tumor-targeting lignads. In addition, combing the gold nanorods, the nanocarriers also provide some advantages, such as photoacoustic tomograpy for in vivo bioimaging for “monitoring” drug delivery. Therefore, the multifunctional drug-carriers is able to be triggered by thermal and magnetic changes, and especially put emphasis on “target” drug-delivery using photoacoustic tomography, cell labeling or others detecting technique.