Explanation of the Anticancer Mechanism and Clinical Chemotherapy for Hybrid Liposomes

杂化脂质体抗癌机制及临床化疗解读

基本信息

批准号：
14350439
负责人：
UEOKA Ryuichi
金额：
$ 9.22万
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：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

Hybrid liposomes can be prepared by simply ultrasonicating a mixture of vesicular and micellar molecules in a buffer solution. The physical properties of these liposomes, such as size, membrane fluidity phase transition temperature, and hydrophobicity can be controlled by changing the composition. In the course of our study, remarkably high inhibitory effects of hybrid liposomes on tumor growth in vitro without drugs have been obtained. No toxicity of the hybrid liposomes was observed in normal cells in vitro and in normal rats in vivo without any side effect.In this study, we report on the uniform and stable hybrid liposomes composed of dimyristoylphosphatidylcholine (DMPC) and polyoxyethylenealkyl ether (C_<12>(EO)n; n=10-25) having inhibitory effects on the growth of tumor cells in vitro, in vivo and clinical chemotherapy.Asummary of the noteworthy aspects of this study is as follows : (a) the uniform and stable structure of hybrid liposomes composed of DMPC and C_<12>(EO)_n was obtained. (b) Highly inhibitory effects of hybrid liposomes were obtained on the growth of many kinds of tumor cells in vitro. (c) Induction of apoptosis by hybrid liposomes through activation of death domains and some kind of caspases was verified for the first time. (d) Significantly prolonged survival was obtained in mice inoculated tumor cells after the treatment with hybrid liposomes without any side effect. (e) In clinical application, the prolonged survival was attained in patient with lymphoma and other tumors after the intravenous injection of hybrid liposomes without drugs and the remarkable reduction of solid tumor was obtained after the local administration of hybrid liposomes.

混合脂质体可以通过在缓冲溶液中简单地超声处理囊泡和胶束分子的混合物来制备。这些脂质体的物理性质，例如尺寸、膜流动性、相变温度和疏水性，可以通过改变组成来控制。在我们的研究过程中，杂合脂质体在体外无需药物的情况下对肿瘤生长具有显着的高抑制作用。杂化脂质体在体外正常细胞和正常大鼠体内均未观察到毒性，无任何副作用。在本研究中，我们报道了由二肉豆蔻酰磷脂酰胆碱（DMPC）和聚氧乙烯烷基醚（C_<12）组成的均匀稳定的杂化脂质体。 >(EO)n; n=10-25) 对体外、体内和临床化疗中肿瘤细胞的生长具有抑制作用。值得注意的方面总结本研究的主要内容如下：(a)获得了由DMPC和C_<12>(EO)_n组成的结构均匀稳定的杂化脂质体。 (b)杂化脂质体在体外对多种肿瘤细胞的生长具有高度抑制作用。 (c)首次验证了混合脂质体通过激活死亡结构域和某种半胱天冬酶诱导细胞凋亡。 (d)用混合脂质体治疗后，接种肿瘤细胞的小鼠的存活率显着延长，且没有任何副作用。 (e)临床应用中，淋巴瘤等肿瘤患者静脉注射杂化脂质体，无需药物即可延长生存期，局部给予杂化脂质体后，实体瘤明显减少。