新型微脂體在腫瘤治療上的潛力

Abstract

藥物之包覆，在生物治療及應用上具其極重要的地位，而今之研究多趨向配合導向分子，將可使藥物更有效率的到達該導向分子標定之目標組織或細胞。本實驗室已開發出一種新型微脂體 (LPPC)，其具有以下特點：(1) 具有奈米化之大小，(2) LPPC可用以包覆藥物，(3) LPPC可有效且穩定吸附蛋白質或胜肽類分子，且由實驗結果可知，先行結合在LPPC上之蛋白質，不為後加入之蛋白質所取代，亦說明其不會被競爭下之特殊性質，(4)此微脂體具可離心之特性。本研究將LPPC包覆藥物 (薑黃素) 之效率及利用此系統治療癌細胞。本研究利用LPPC包覆薑黃素 (curcumin) 而形成curcumin/LPPC，此複合物對於curcumin-sensitive cells可增加5倍的細胞毒性，並對curcumin-resistant cells則可增加約20倍的細胞毒性，其主要原因可能為LPPC可快速的將curcumin運送並累積在腫瘤細胞當中。

The research of drug- delivery system is an important topic on treatment of cancer. Using targeting molecules to improve drug delivery efficiency is a tendency in recent studies. We have developed a novel liposome called Lipo-PEI-PEG complex (LPPC), and the results showed four properties of LPPC: (1) LPPC is a nano-particle. (2) LPPC has ability for drug encapsulation. (3) LPPC can adsorb proteins or peptides effectively and stably. Moreover, we also demonstrated that the protein adsorbed at first time by LPPC cannot be competed by other proteins added later. This special property is the first time to be developed. And, (4) LPPC can be precipitated by centrifugation. Therefore, the purposes of this study are to measure the quantity of drug (curcumin) encapsulated by LPPC, and to utilize this system to treat cancer cells, LPPC was used as a carrier for the encapsulation of curcumin to give curcumin/LPPC. The cytotoxic activity of the curcumin/LPPC was 5-fold higher than curcumin when tested on curcumin-sensitive cells and 20-fold more active against curcumin-resistant cells. The increased cytotoxic activity of curcumin/LPPC is likely attributable to its rapid accumulation in the cell.