超分子水凝膠在抗癌奈米藥物之應用

Abstract

隨著奈米科學與奈米科技的新知快速進展而產生了新的研究領域，這個領域可以 提供許多機會研發新的藥物來治療癌症以及改善人類的生活品質。到目前為止， 以奈米科技為中心的研究領域在生醫方向上已經有一些明顯的成果，例如在藥物 輸送載體以及新的治療方法方面。因此，我們希望更進一步的發展利用酵素催化 使小分子可以在細胞內自組裝產生含藥物的奈米纖維結構。我們提出利用含抗癌 藥物水凝膠因子在細胞內自組裝來對抗多重抗藥性以及增加局部性藥物濃度來 提高與目標物的作用力，這個新方法可能提供在臨床上可以用來處理有抗藥性癌 症的解決方法。此外，研究利用酵素來產生奈米纖維是一個新的方法來發展抗癌 奈米藥物。本計畫將利用酵素使含抗癌藥物的超分子水凝膠產生自組裝奈米藥物 來治療癌症，我們計畫達成三個主要目標，而透過這樣的研究將可以提供一個合 邏輯的方式讓我們達到最後目的-發展新的奈米藥物。第一個目標將致力於發展 含螢光團的胜肽分子來產生新的螢光超分子水凝膠。第二個目標將整合抗癌藥物 到可自組裝的螢光超分子水凝膠分子結構中以及研究含抗癌藥物的奈米纖維的 細胞反應。第三個目標將嘗試把光敏劑合併到自組裝奈米纖維中以及評估在癌細 胞內光動力治療效果。我們相信本計畫的成功將會開啟一個發展抗癌奈米藥物的 全新方法

The rapid growth of new knowledge in nanoscience and nanotechnology is extending new research frontiers and offering exceptional opportunities of creating new generation of diagnostics and therapeutics to treat cancer and improve the quality of human life. The considerable research interests in the area have already made significant progresses, such like drug delivery carriers and new treatment protocols. Therefore, we wish to further develop enzyme catalysis that triggers the self-assembly of small molecules to form drug-decorated nanofibers inside cancer cells. We propose that intracellular self-assembly of the anticancer drug molecules will overcome multidrug resistance (MDR) by avoiding the efflux pumps and increasing the local concentration of drugs for enhance binding to the targets and may offer a new clinical solution for the treatment of drug resistance cancers. Besides, the investigation of enzymatic formation of molecular nanofibers is a new approach for developing anticancer nanomedicine. The present work will focus on the usage of self-assembly and enzyme catalysis to create molecular nanofibers by supramolecular hydrogelators as novel nanomedicines for anticancer therapy. Three specific aims will be investigated and that will provide a logical approach for us to reach the final goal – development of new nanomedicine. The first aim focuses on the development of fluorophore-capped peptides as new supramolecular hydroglators. The second aim is to combine anticancer drug into the structure of hydrogelator and study the effects of the drug-containing nanofibers formed inside cells for inducing cell death. The third aim deals with the photosensitizer-containing nanofibers for evaluating their photodynamic functions, and effectiveness inside cells. We believe the success of the proposed research will open up a new strategy for the development of anticancer nanomedicines.