Antitum of Mechanism of Hybrid Liposomes and Clinical Application

1.杂化脂质体的抗肿瘤机制我们研究了杂化脂质体诱导细胞凋亡的线粒体途径。加入杂合脂质体后线粒体膜电位降低，提示杂合脂质体可能通过线粒体诱导细胞凋亡。免疫印迹法检测细胞色素c的释放和caspase-9的活化。Caspase-9抑制剂的浓度依赖于DNA凋亡率。这些结果表明，复合脂质体可能通过线粒体和caspase-9.2的激活来诱导细胞凋亡。含糖表面活性剂的三组分复合脂质体的抑制作用我们首次成功地合成了糖型胶束表面活性剂--乳糖烷基酰胺(LacCn)。将L-α-二肉豆蔻基磷脂酰胆碱(DMPC)、吐温20和LaCn(DMPC：Tween20：LaCn=65：7：28)的混合物超声破碎后，得到球形囊泡，即三组分复合脂质体。值得注意的是，高…DMPC、Tween20和LacCn(DMPC：Tween20：LacCn=65：7：28)组成的三组分杂化脂质体对体外培养的人脑胶质瘤(U251)和肺腺癌(RERF-LC-OK)细胞的生长无明显抑制作用，但未发现任何单一组分(DMPC、Tween20、LacCn)或DMPC和Tween20两组分杂化脂质体对肿瘤细胞生长的抑制作用。生物伦理学委员会通过后，未服用任何药物。每天静脉注射混合脂质体。血常规、血生化检查均未见异常。静脉注射杂化脂质体可延长淋巴瘤患者的生存期，且无任何副作用；局部注射杂合脂质体可使肿瘤(实体瘤)明显减少。这种不含药物的杂化脂质体在临床上的成功应用在世界上尚属首次。较少

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