Targeting thermo-chemotherapy for malignant brain tumor using thermosensitive liposome and local hyperthermia

使用热敏脂质体和局部热疗进行恶性脑肿瘤的靶向热化疗

• 批准号: 05454394
• 负责人: TANAKA Ryuichi
• 金额: $ 4.16万
• 依托单位: NIIGATA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454394/
• 关键词: thermosensitive liposome; thermochemotherapy; malignant brain tumor; targeting therapy; 温熱化学療法; ターゲッティング療法

Malignant glioma responds poorly to chemotherapy presumably mainly because the antitumor drugs can not be delivered in effective concentrations to the tumor site without causing complications, and because the existence of the blood-brain barrier (BBB) restricts the distribution of many antitumor drugs to malignant gliomas. We used thermosensitive liposomes containing CDDP(CDDP-liposome) with localized heating, and the possibilities of this drug delivery system to the brain tumor were discussed. First, this unique and attractive strategy showed remarkable effects against the subcutaneous tumor. The authors then investigated the antitumor effect on rat malignant brain tumor. The brain tumor heating was given using a radiofrequency antenna which was designed at our institute. As a result, the rats treated by CDDP-liposome+hyperthermia had the longest survival time, and the tumor CDDP level of this group was the highest when compared to other groups. These findings suggest that the combination of thermosensitiveliposome and localized hyperthermia could 1)bring a direct thermal killing of the tumor cells, plus 2)increase a permeability of the BBB to transport of CDDP,plus 3)target CDDP-liposomes to the tumor site and produce an effective release of liposomal CDDP with greater activity than when free CDDP was infected .

恶性胶质瘤对化疗反应差，可能主要是因为抗肿瘤药物不能以有效浓度递送到肿瘤部位而不引起并发症，并且因为血脑屏障（BBB）的存在限制了许多抗肿瘤药物在恶性胶质瘤中的分布。我们采用局部加热的温敏性顺铂脂质体（CDDP-liposome），并探讨了这种给药系统用于脑肿瘤的可能性。首先，这种独特而有吸引力的策略对皮下肿瘤显示出显着的效果。作者还研究了其对大鼠恶性脑肿瘤的抗肿瘤作用。脑肿瘤加热是使用射频天线，这是在我们的研究所设计。结果表明，CDDP脂质体+热疗组大鼠生存时间最长，肿瘤CDDP水平最高。这些发现表明，热敏脂质体和局部热疗的组合可以1）带来对肿瘤细胞的直接热杀死，加上2）增加血脑屏障对CDDP转运的渗透性，加上3）将CDDP-脂质体靶向肿瘤部位并产生比当游离CDDP被感染时具有更大活性的脂质体CDDP的有效释放。

项目成果

K.Kakinuma: "Drug delivery to the brain using thermosensitive liposome and local hyperthermia" International Journal of Hyperthermia. 12. 157-165 (1996)

K.Kakinuma：“使用热敏脂质体和局部热疗将药物输送到大脑”《国际热疗杂志》。

柿沼 健一: "熱感受性liposomeと局所温熱療法を用いた悪性脳腫瘍に対するTargeting療法(第2報)" 新潟大学脳研究所業績集. 25. 91 (1992)

Kenichi Kakinuma：“使用热敏脂质体和局部热疗对恶性脑肿瘤进行靶向治疗（第二次报告）”新泻大学脑研究所论文集。25. 91（1992）。

柿沼 健一: "Targeting Chematherapy for malignant brain tumor using thermosensitive liposme and local hyperthermia" 新潟大学脳研究所業積集. 26. 85 (1993)

Kenichi Kakinuma：“使用热敏脂质和局部热疗对恶性脑肿瘤进行靶向化疗”，新泻大学脑研究所论文集，26. 85 (1993)。

K.Kakinuma: "Antitumor Effect of CDDP-entrapping Thermosensitive Liposome Combined with Local hyperthermia against Rat Malignant Glioma" Hyperthermic Oncology in Japan '93. 197-198 (1995)

K.Kakinuma：“CDDP 包埋热敏脂质体结合局部热疗对大鼠恶性胶质瘤的抗肿瘤作用”日本高温肿瘤学 93。

高橋 英明: "脳腫瘍に対する温熱治療のための温度シミュレーション-二次元有限要素解析によるcomputersimulation-" Jpn.J.Hyperthermic Oncol.11. 356-364 (1995)

Hideaki Takahashi：“脑肿瘤热治疗的温度模拟 - 使用二维有限元分析的计算机模拟”Jpn.J.Hyperthermic Oncol.11（1995）。