新型微脂體的開發及應用

Abstract

藥物運送一直是醫藥工程發展的熱門主題之一，有效的藥物運送可以降低藥物使用藥量，並同時提高病灶區治療的效果，進而達到降低副作用的目的。近年來，標靶藥物的發展更是醫學工程發展的重點，研究者希望透過有效的製造專一性的標靶藥物，以達到治療特定目標細胞之目的，也因如此，許多不同的載體因應而生，而其中微脂體為主要發展的載體之一。為了達到專一性運送治療性藥物至特定細胞，微脂體表面會利用抗體、專一性胜肽，或是人工化單株抗體加以修飾，使得微脂體的專一性大大提升。然而，這樣的修飾過程往往會運用到化學鍵結的方式，如此一來，加以修飾的專一性蛋白之活性或是功能則可能受到傷害，為了解決專一性蛋白活性下降的問題，非共價結合的載體則開始被研究，但卻因為非共價的吸附力不穩定，而造成發展上的阻礙。基於上述，本研究的目的為開發一種新型的微脂體 (LPPC)，其可利用穩定非共價鍵結與蛋白質結合，且吸附在其上的蛋白質仍然保有其活性，並進一步利用此微脂體結合不同之蛋白而進行應用，如周邊血液單核球細胞的活化、非共價性酵素連結之免疫吸收分析 (ELISA)。基於上述之特性，本研究更進一步利用此新型微脂體將蛋白質運送到細胞內，由研究發現，此微脂體可有效運送蛋白質進入到細胞中，且運送進入的蛋白質仍然可保有其酵素的活性，此特性可有效的幫助重組蛋白運送到細胞中以達到治療的目的。

Drug delivery system is under active evolution in the field of medicine engineering. Efficient drug delivery can improve the efficacy of therapeutic drug in the focus of disease with the lower dosage of supplied drug. Targeting drug is currently under active development in the field of drug delivery system. With the combination of targeting molecules, therapeutic drugs can be transport to targeted cell. Liposomal delivery systems are one of the developed transporting carriers. To improve the specific targeting ability, surface of liposome are modified with targeting molecules, such as antibody, targeting peptide, and artificial monoclonal antibody. However, most of the currently available targeting vectors are produced via the linkage of targeting molecules, and the activity of certain targeting molecules may attenuate by covalent linkage. One way to avoid this drawback involves the noncovalent adhesion of targeting molecules to a cationic liposome. In order to improve the weak interactions between the targeting molecules and liposomes by noncovalent interaction, a novel liposome (LPPC) is developed in this study. The LPPC can stably capture the targeting proteins via a noncovalent linkage without defluxion, and the bound protein can retain its activity. Therefore, LPPC are further applied in various applications, such as cell signaling, cell profiling, noncovalent enzyme linked immunoassays. Based on the descriptions above, we utilize the LPPC as protein transporter to deliver the proteins into the cells. According the results, LPPC can efficiently deliver the proteins into the cells and the transported protein can retain its enzymatic activity. Therefore, the intracellular protein transported by LPPC will be a potent and effective method to the biological and clinical researches.