設計與製備具顯影、標靶與即時監測藥物釋放之多功能奈米藥物輸送載體

Abstract

癌症，早已成為全球人類的頭號殺手。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。本研究計畫主要是 根據先前對於氧化鐵單晶殼層薄膜的成長機制、微觀結構及奈米形變的研究成果。進一 步提出一些前瞻及創新性的研究構想，來進行多功能奈米藥物輸送載體的研發，包括 (i) 將所研發之氧化鐵單晶殼層薄膜的成長概念應用於有機高分子及無機中孔洞silica 的奈 米藥物載體上來是否可達到零釋放及可控制藥物釋放。(ii)並經由製程的修改來探討包覆 親疏水性藥物的特性及藥物釋放行為(iii) 進一步將低毒性具發光學特性的量子點銅銦 硫(CIS)，架接於奈米藥物載體的表面上，可以利用其螢光顯影，來追蹤該奈米藥物載體 及細胞，(iv)利用外部的磁場來研究磁場效應對於具有磁敏感性及量子發光的奈米結構 的藥物控制局部釋放，(v)透過磁場來操控有機及無機奈米磁量子藥物載體的藥物釋放模 式及釋放量與量子點螢光強度的變化，以分析其彼此間的相互關係，進而可用來評估藥 物即時釋放量及模式對於腫瘤的影響。(vi)透過奈米藥物載體的表面改質，來進行癌細 胞之標靶，以探討奈米藥物載體進入癌細胞的效率。預定在這三年的研究計畫，將利用 材料與藥物的結合，針對此具有磁敏感性之多功能奈米藥物載體元件的合成製程，奈米 粒子的物理及磁性與量子點的光學特性及細胞毒性，藥物釋放及操控與癌細胞標靶等， 進行相關重要的研究，設計與製備一種具多功能性的奈米藥物載體，此奈米載體具有藥 物操控釋放、顯影與標靶之奈米複合藥物載體，搭配外加磁場的控制，期望在未來可以 同步追蹤癌細胞及即時偵測藥物釋放的情形，以評估是否可達最佳治療效果的新世代標 靶治療的需求。

Nanotherapeutic carriers and associated therapeutic methodologies have been the subject of many studies. Great attention has recently been paid to carriers with multifunctionality, including imaging, controlled drug release, and targeting, in order to achieve better therapeutic efficacy with higher resolution. This research focuses on design and development of a multifunctional drug delivery nanodevice. The device integrates nano-imaging, targeting, and controlled drug delivery, as well as the capability to monitor, in-situ, the amount of drug released from the nanodevice with single-cell resolution. The nanodevice is composed of a polymer core/single-crystal iron oxide shell nanostructure bonded to a quantum dot. It shows outstanding release and retention characteristics via an external on/off manipulation of a high-frequency magnetic field. The quantum dot bonded to the nanodevice provides optical information for in-situ monitoring of the drug release through use of a magnetic field. It has been quantitatively determined that there is a linear decrease in optical intensity of the quantum dot with drug release. Remote control drug release from the nanodevice in a cancerous cell line (i.e., HeLa) was successfully accomplished using the same induction scenario. When nanodevices equipped with quantum dots are taken into cancerous cells, they are able to provide real-time drug dose information through corresponding variation in emission spectrum. The nanodevice designed in this study has achieved its potential as a cell-based drug delivery system for nanotherapeutic applications via remote controlled drug release and in-situ monitoring capabilities.