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A new chemothermotherapy focusing to the tumor invading zone of malignant glioma by thermosensitive liposome

热敏脂质体针对恶性胶质瘤肿瘤侵袭区的新型化疗

基本信息

批准号：
09557115
负责人：
TANAKA Ryuichi
金额：
$ 4.67万
依托单位：
NIIGATA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09557115/
关键词：
thermosensitive liposome malignant glioma chemotherapy hyperthermia tumor invading zone adriamycin

项目摘要

The area surrounding the core of malignant glioma was already infiltrated by tumor cells ( tumor invading zone ) and was commonly unresectable resulting in its regrowth and poor prognosis. However, up to date, there have been few attempts to focus the treatment of this tumor invading zone. We developed a new targeting chemo-thermotherapy focusing to the tumor core, and also to the tumor invading zone. Thermosensitive liposomes are microscopic vesicles that can contain drugs and release them effectively in response to hyperthermia. Our hyperthermic treatment, above 42 - 43 ℃, can treat the entire tumor core of human malignant glioma for direct thermal killing. When heating, the 40 ℃ area extended up to a wide portion, covering the tumor invading zone. Therefore, new thermosensitive liposomes containing Adriamycin ( ADR ) were prepared to release their content at 40 ℃ and above. Consequently, this new thermosensitive liposome sharply released ADR as planned, and high concentrations of ADR was focused in both rat brain tumor ( >42 ℃ ) and the surrounding brain tissue which corresponds to the tumor invading zone ( at 42 - 40 ℃ ). These results suggest that this new procedure 1) helps to deliver the antitumor drugs selectively and wider : to the tumor core, and also to the tumor invading zone, 2) shows no thermal damages of normal brain tissue in the tumor invading zone with lower temperatures, 3) permits ADR and other antitumor drugs to be used regardless the BBB problem, 4) contributes to the synergistic effect of antitumor drugs and hyperthermia. This new liposomal therapy can be used clinically as a superior targeting chemo-thermotherapy of malignant gliomas.

恶性胶质瘤核心周围已被肿瘤细胞浸润（肿瘤浸润区），通常不能切除，导致其复发和预后不良。然而，迄今为止，很少有人尝试集中治疗这种肿瘤侵入区。我们开发了一种新的靶向化疗热疗，既聚焦于肿瘤核心，也聚焦于肿瘤浸润区。温敏脂质体是一种微小的囊泡，它可以容纳药物并在高温下有效释放药物。我们的热疗，在42 - 43 ℃以上，可以治疗人恶性胶质瘤的整个瘤核，进行直接热杀伤。当加热时，40 ℃区域延伸到较宽的部分，覆盖肿瘤浸润区。因此，制备了阿霉素（ADR）温敏脂质体，使其在40 ℃以上释放。结果表明，这种新型温敏脂质体能按计划迅速释放ADR，高浓度ADR集中在大鼠脑肿瘤（>42 ℃）和肿瘤浸润区周围脑组织（42 ~ 40 ℃）。这些结果表明，这种新方法1）有助于选择性和更广泛地递送抗肿瘤药物：对肿瘤核心，以及对肿瘤侵袭区，2）显示在较低温度的肿瘤侵袭区中正常脑组织没有热损伤，3）允许使用ADR和其它抗肿瘤药物而不管BBB问题，4）有助于抗肿瘤药物和热疗的协同作用。这种新的脂质体治疗方法可作为恶性胶质瘤的一种上级靶向热化疗方法应用于临床。