Development of intracellular targeting liposomes for boron neutron-capture therapy

用于硼中子捕获治疗的细胞内靶向脂质体的开发

• 批准号: 13470190
• 负责人: MARUYAMA Kazuo
• 金额: $ 9.22万
• 依托单位: Teikyo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470190/
• 关键词: Neutron-Capture Therapy; DDS; Liposome; Transferrin

The successful treatment of cancer by BNCT requires the selective concentration of ^<10>B within malignant tumor cells. Intracellular targeting ability and cytotoxic effects of ^<10>B entrapped TF-PEG-liposomes, in which TF is covalently linked to the distal terminal of PEG chains on the external surface of PEG-liposomes, were examined in Colon 26 tumor-bearing mice. TF-PEG-liposomes readily bound to tumor cells in vitro, and were internalized by receptor-mediated endocytosis. ^<10>B-PEG-liposomes and ^<10>B-TF-liposomes showed prolonged residence time in the circulation and low RES uptake in tumor-bearing mice, resulting in enhanced extravasation of the liposomes into the solid tumor tissue and reached high level of ^<10>B content in tumor. After thermal neutron irradiation of mice injected with ^<10>B-PEG-liposomes or ^<10>B-TF-liposomes, tumor growth was suppressed relative to controls. These results suggest that intravenous injection of ^<10>B TF-PEG-liposome can increase the intracellular retention of ^<10>B atoms, which were introduced by receptor mediated endocytosis after binding, causing tumor growth suppression in vivo upon thermal neutron irradiation.

通过BNCT成功治疗癌症需要在恶性肿瘤细胞内选择性地浓缩^ 10 B。在结肠26荷瘤小鼠中检查10B包埋的TF-PEG-脂质体的细胞内靶向能力和细胞毒性作用，其中TF共价连接至PEG-脂质体外表面上的PEG链的远端。 TF-PEG-脂质体在体外很容易与肿瘤细胞结合，并通过受体介导的内吞作用内化。 ^ 10 B-PEG-脂质体和^ 10 B-TF-脂质体在荷瘤小鼠中显示出循环中的滞留时间延长和RES摄取较低，导致脂质体向实体瘤组织中的外渗增强，并在肿瘤中达到高水平的^ 10 B含量。对注射了 10 B-PEG-脂质体或 10 B-TF-脂质体的小鼠进行热中子照射后，相对于对照，肿瘤生长受到抑制。这些结果表明，静脉内注射 10 B TF-PEG-脂质体可以增加 10 B 原子的细胞内保留，其在结合后由受体介导的内吞作用引入，在热中子照射时引起体内肿瘤生长抑制。

项目成果

H.Tinuma, et al.: "Intracellular Targeting Therapy of Cisplatin-Encapsulated Transferrin-PEG-Liposome on Peritoneal Dissemination of Gastric Cancer"Int. J. Cancer. 99. 130-138 (2002)

H.Tinuma等人：“顺铂封装的转铁蛋白-PEG-脂质体对胃癌腹膜播散的细胞内靶向治疗”Int。

T.Mizoue et al.: "Targetability and intracellular delivery of anti-BCG antibody-modified, pH-sensitive fusogenic immunoliposomes to tumor cells"Int.J.Pharm.. 237. 129-137 (2002)

T.Mizoue 等：“抗 BCG 抗体修饰的 pH 敏感融合免疫脂质体对肿瘤细胞的靶向性和细胞内递送”Int.J.Pharm.. 237. 129-137 (2002)

Kazuo Maruyama et al.: "Targeting of post-ischemic cerebral endothelium in rat by liposomes bearing polyethylene glycol-coupled transferrin"Neurol.Res.. (印刷中). (2002)

Kazuo Maruyama 等人：“携带聚乙二醇偶联转铁蛋白的脂质体靶向大鼠缺血后脑内皮”Neurol.Res.（印刷中）。

Kazuo Maruyama et al.: "Targetability and intracellular delivery of anti-BCG antibody-modified, pH-sensitive fusogenic immunollposomes to tumor cells"Int.J.Pharm.. 237. 129-137 (2002)

Kazuo Maruyama 等：“抗 BCG 抗体修饰的 pH 敏感性融合免疫脂质体对肿瘤细胞的靶向性和细胞内递送”Int.J.Pharm.. 237. 129-137 (2002)

Kazuo Maruyama et al.: "Neutron capture autoradiography for a study on boron neutron capture therapy"Radiation Measurement. 34. 555-558 (2001)

Kazuo Maruyama 等人：“中子俘获放射自显影术用于硼中子俘获疗法的研究”辐射测量。