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

• 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
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14350439/
• 关键词: Hybrid Liposomes; Anticancer Mechanism; Clinical Chemotherapy; Dimyristoylphosphatidylcholine; No Side Effect; Caspases; Apoptosis; Life Prolongation; 担がんマウス; 肝臓がん; 膜融合; 悪性黒色腫

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.

只需在缓冲溶液中对囊泡分子和胶束分子的混合物进行超声波处理，即可制备出复合脂质体。这些脂质体的物理性质，如大小、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，杂化脂质体在没有药物的情况下，在体外对肿瘤生长有显著的抑制作用。在本研究中，我们报道了由二甲基磷脂酰胆碱(DMPC)和聚氧乙烯基烷基醚(C_&lt；12&gt；(EO)n；n=10-25)组成的均匀稳定的杂化脂质体，它在体外、体内和临床化疗中对肿瘤细胞的生长都有抑制作用。(2)杂化脂质体对多种肿瘤细胞的体外生长均有较强的抑制作用。(C)首次证实了复合脂质体通过激活死亡结构域和某些caspase诱导细胞凋亡。(D)经复合脂质体治疗后，接种肿瘤细胞的小鼠存活时间显著延长，且无任何副作用。(5)在临床应用中，静脉注射杂化脂质体可延长淋巴瘤等肿瘤患者的生存期，局部给药后实体瘤明显减少。

项目成果

Hybrid Liposomes as a Drug Carrier for the Oral Administration of Insulin in Diabetic Rats

混合脂质体作为糖尿病大鼠口服胰岛素的药物载体

• 发表时间: 2004
• 期刊: YAKUGAKU ZASSHI vol.124 No.4
• 作者: K.Nakashima;M.Miyagi;K.Goto;Y.Matsumoto;R.Ueoka
• 通讯作者: R.Ueoka

Hideaki nagami: "Induction of Apoptosis by Hybrid Liposomes without Antitumor Drugs toward Human Breast Tumor Cells"Journal of Chemical Engineering of Japan. 36・9. 1127-1129 (2003)

Hideaki nagami：“不使用抗肿瘤药物的混合脂质体对人乳腺肿瘤细胞的凋亡诱导”日本化学工程学报36・9（2003）。

Kentaro Nakashima: "Enzymatic and Hyperglycemia Stability of Chemically Modified Insulins with Hydrophobic Acyl Groups"Bioorganic & Medicinal Chemistry Letters. 14・4. 481-483 (2003)

中岛健太郎：“疏水酰基化学修饰胰岛素的酶促稳定性和高血糖稳定性”《生物有机与药物化学快报》14・4（2003 年）。

蛋白質 核酸 酵素 増刊号 科学と生物学の接点がつくるNEWバイオテクノロジー「アポトーシス誘導ハイブリッドリポソームのがん治療効果」

蛋白质核酸酶特刊科学与生物学交叉创造的新生物技术“诱导细胞凋亡的混合脂质体的癌症治疗作用”

• 发表时间: 2003
• 作者: Yoshio Suzuki;Hirokazu Komatsu;Takafumi Ikeda;Naohiko Saito;Sawa Araki;Daniel Citterio;Hideaki Hisamoto;Yoshiichiro Kitamura;Takeshi Kubota. Jun Nakagawa;Kotaro Oka;Koji Suzuki;松本 陽子
• 通讯作者: 松本 陽子

生体内の高分子 機能材料開発と医療への新展開「リポソームによる癌治療」

体内高分子功能材料开发及医学新进展“利用脂质体治疗癌症”

• 发表时间: 2003
• 作者: 上岡 龍一