标题: | 新型微脂体的开发及应用 Development and application of a novel |
作者: | 刘彦谷 Liu, Yen-Ku 廖光文 Liao, Kuang-Wen 分子医学与生物工程研究所 |
关键字: | 微脂体;导向分子;非共价性作用;蛋白载体;liposome;targeting molecule;noncovalent interaction;protein carrier |
公开日期: | 2010 |
摘要: | 药物运送一直是医药工程发展的热门主题之一,有效的药物运送可以降低药物使用药量,并同时提高病灶区治疗的效果,进而达到降低副作用的目的。近年来,标靶药物的发展更是医学工程发展的重点,研究者希望透过有效的制造专一性的标靶药物,以达到治疗特定目标细胞之目的,也因如此,许多不同的载体因应而生,而其中微脂体为主要发展的载体之一。为了达到专一性运送治疗性药物至特定细胞,微脂体表面会利用抗体、专一性胜肽,或是人工化单株抗体加以修饰,使得微脂体的专一性大大提升。然而,这样的修饰过程往往会运用到化学键结的方式,如此一来,加以修饰的专一性蛋白之活性或是功能则可能受到伤害,为了解决专一性蛋白活性下降的问题,非共价结合的载体则开始被研究,但却因为非共价的吸附力不稳定,而造成发展上的阻碍。基于上述,本研究的目的为开发一种新型的微脂体 (LPPC),其可利用稳定非共价键结与蛋白质结合,且吸附在其上的蛋白质仍然保有其活性,并进一步利用此微脂体结合不同之蛋白而进行应用,如周边血液单核球细胞的活化、非共价性酵素连结之免疫吸收分析 (ELISA)。基于上述之特性,本研究更进一步利用此新型微脂体将蛋白质运送到细胞内,由研究发现,此微脂体可有效运送蛋白质进入到细胞中,且运送进入的蛋白质仍然可保有其酵素的活性,此特性可有效的帮助重组蛋白运送到细胞中以达到治疗的目的。 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. |
URI: | http://140.113.39.130/cdrfb3/record/nctu/#GT079529803 http://hdl.handle.net/11536/41266 |
显示于类别: | Thesis |