自組裝水凝膠在生物顯影與藥物載體之應用

Abstract

隨著奈米科學與奈米科技的迅速進展因而提供許多研發新藥的機會來治療癌症以及改 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。在最近四十年來，成像科 學的發展也延伸到新藥的發現與發展，因此，在本計畫中，我們希望更進一步的發展利 用有機合成產生螢光基團-胜肽基團-抗癌藥物的分子結構來發展由自組裝產生的螢光 水凝膠抗癌藥物。我們提出利用螢光水凝膠藥物可以因為增加藥物的局部濃度來提高抗 癌效果並預期可以抑制腫瘤的生長與轉移，我們選用的螢光基團有著與艾黴素藥物類似 的吸光與放光波長將預期可以增加觀測螢光藥物在活體中的靈敏度。本計畫將利用將著 重在合成含螢光的超分子水凝膠藥物並利用自組裝產生水凝膠藥物來治療癌症，我們計 晝將達成兩個主要目標，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，這些螢光基團在500-600奈米之間有著很強的螢光，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這些水凝膠藥物在 生物體中的作用，例如藥物分布與累積。透過這樣的研究，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。

Rapid development of new knowledge in nanoscience and nanotechnology is 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 as drug delivery carriers and new treatment protocols. Besides, imaging sciences have also grown exponentially within the past four decades and many technologies have become indispensable in clinical use. Recently, imaging technologies and imaging probes for humans are now extending the applications of molecular imaging further into drug discovery and development. In this proposal, we wish to further develop new nanomedicines by the self-assembly of hydrogelators with the structure of fluorophore-peptide-drug. We propose that self-assembly of the hydrogelators will administrated into solid tumors to hinder their growths and prevent their metastasis by increasing the local concentration of drugs. The selected fluorophores have similar intense absorption and emission as those of doxorubicin drug which may result in higher contrast for bioimaging applications. The present work will focus on the synthesis of new hydrogelators and usage of self-assembly to create molecular nanofibers by supramolecular hydrogelators as novel nanomedicines for anticancer therapy. Two specific aims will be investigated and that will provide a logical approach for us to develop new nanomedicines. The first aim focuses on the development of fluorophore-capped peptides as new supramolecular hydroglators. These fluorophores hold intensive emissions in the range of 500-600 nm. The second aim is to combine anticancer drug into the structure of hydrogelator and study the effects of the drug distribution and accumulation by molecular imaging. We believe the success of the proposed research will open up a new strategy for the development of anticancer nanomedicines.