Antitum of Mechanism of Hybrid Liposomes and Clinical Application

杂化脂质体的抗癌作用机制及临床应用

基本信息

批准号：
12555232
负责人：
UEOKA Ryuichi
金额：
$ 6.4万
依托单位：
Sojo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

1. Antitumor Mechanism of Hybrid LiposomesWe examined mitochondrial pathway for apoptosis induced by hybrid liposomes. Mitochondrial membrane potential was decreased by adding hybrid liposomes, suggesting that hybrid liposomes should induce apoptosis through mitochondria. Release of cytochrome c and activation of caspase-9 were observed using western blotting analysis. Concentration dependence of caspase-9 inhibitor on the apoptotic DNA rates was also obtained. These results suggest that hybrid liposomes should induce apoptosis through mitochondria and activation of caspase-9.2. Inhibitory Effects of Three-Component Hybrid Liposomes Including Sugar SurfactantsWe successfully produced sugar-type micellar surfactants, lactonoalkylamide (LacCn), for the first time. Spherical vesicles, three-component hybrid liposomes, were obtained after sonication of mixture of L-α-dimyristoylphosphtidylcholine (DMPC), Tween 20 and LacCn (DMPC : Tween 20 : LacCn = 65 : 7 : 28). It is noteworthy that high … More inhibitory effects of the three-component hybrid liposomes composed of DMPC, Tween 20, and LacCn (DMPC : Tween 20 : LacCn = 65 : 7 : 28) on the growth ofglioma (U251) and lung adenocarcinoma (RERF-LC-OK) cells were attained in vitro without any drug, although no significant inhibitory effects of any individual component (DMPC, Tween 20, LacCn) or the two-component hybrid liposomes of DMPC and Tween 20 on the growth of tumor cells examined were obtained.3.Clinical Application of Hybrid LiposomesPatients with lymphoma were selected for the clinical application of hybrid liposomes composed of DMPC and C_<12>(EO)_<23> without any drug after passing the committee of bioethics. The hybrid liposomes were administered intravenously every day. There were not abnormal findings on routine blood test and hematochemistry. Prolonged survival was attained in patient with lymphoma after the intravenous injection of hybrid liposomes without any side effect and the remarkable reduction of neoplasm (solid tumor) was obtained after the local administration of hybrid liposomes. Such a successful clinical application of hybrid liposomes without drugs was for the first time in the world. Less

1. 混合脂质体的抗肿瘤机制我们检查了混合脂质体诱导细胞凋亡的线粒体途径。通过添加混合脂质体，线粒体膜电位降低，表明混合脂质体应该通过线粒体诱导细胞凋亡。使用观察到细胞色素c的释放和caspase-9的激活。还获得了 caspase-9 抑制剂对 DNA 凋亡率的浓度依赖性。这些结果表明混合脂质体。应该通过线粒体诱导细胞凋亡并激活caspase-9.2 包括糖表面活性剂的三组分混合脂质体的抑制作用我们首次成功生产了糖型胶束表面活性剂内酯烷基酰胺（LacCn），三组分混合脂质体。 L-α-二肉豆蔻酰磷脂酰胆碱混合物超声处理后获得(DMPC)、Tween 20 和 LacCn (DMPC : Tween 20 : LacCn = 65 : 7 : 28) 值得注意的是，由 DMPC、Tween 20 和 LacCn 组成的三组分混合脂质体具有高抑制作用。 DMPC : Tween 20 : LacCn = 65 : 7 : 28) 对神经胶质瘤 (U251) 和肺生长的影响尽管任何单独组分（DMPC、Tween 20、LacCn）或 DMPC 和 Tween 20 的双组分混合脂质体对腺癌细胞 (RERF-LC-OK) 的生长没有显着抑制作用，但在没有任何药物的情况下在体外获得了腺癌细胞 (RERF-LC-OK)。 3.混合脂质体的临床应用选取淋巴瘤患者进行DMPC和DMPC组成的混合脂质体的临床应用。 C_<12>(EO)_<23>通过生物伦理委员会后，每天静脉注射混合脂质体，常规血液检查和血液化学检查均未发现异常，淋巴瘤患者获得了延长的生存期。静脉注射混合脂质体后无任何副作用，局部给药后肿瘤（实体瘤）显着减少，获得了如此成功的混合脂质体临床应用。不含药物的脂质体在世界上尚属首次。