在此項研究中，我們設計一個具有專一性傳遞與增加藥物在細胞內累積量的長效型艾黴素(DOX)載體。從先前的研究中發現，IL類似物可攜帶小分子螢光物質FITC進到細胞裡; 根據這樣的發現，我們進一步想利用此條胜肽與小分子藥物-艾黴素進行共價接合增加攜帶藥物進入癌細胞中的累積量。更進一步，我們將一具有生物相容性的高分子聚乙二醇(polyethylene glycol, PEG) 藉以保護胜肽，避免酵素將胜肽切割進而達到延長體內循環的時間。此外我們也設計一段蛋白酶分解片段，使載體能在特定細胞周圍釋放。研究結果中發現，在聚乙二醇保護下，切割一定量的胜肽從十分鐘延長至四小時，可證明聚乙二醇可有效的保護胜肽。同時，在蛋白酶切割後，我們觀察到藥物在細胞內累積量上升。因此，我們認為此一藥物載體設計可應用於實際藥物傳遞，並且能增進藥物的累積量。;In this study, we designed and synthesized the novel doxorubicin (DOX) formulation for enhanced drug delivery and cancer cell targeting. An Indolicidin analogue was covalently conjugated to DOX and acted as a transmembrane carrier for enhancing drug translocation into HepG2 cells. The bioinert polymer, polyethylene glycol (PEG), was conjugated with peptide for prolonging in vivo drug circulation. The protease cleavable sequences were designed for cancer cell recogition. The PEG segment could be detached from DOX-peptide in the presence of protease. It was found that the half-life in trypsin after PEG protection could be increased from 10 minutes to 4 hours. And the enhanced penetration could be observed after protease cleavage. Thus, this DOX formulation is able to be a potential to apply in pharmaceutical use.
