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.

恶性胶质瘤的核心周围区域已被肿瘤细胞浸润（肿瘤侵袭区），通常无法切除，导致其再生和预后不良，但迄今为止，针对这种侵袭性肿瘤的治疗还鲜有尝试。我们开发了一种新的靶向化疗热疗法，重点针对肿瘤核心，并且热敏脂质体是可以容纳药物并释放药物的微小囊泡。我们的热疗，在42-43℃以上，可以对人类恶性胶质瘤的整个瘤核进行直接热杀伤。加热时，40℃的区域扩大到很宽的部分，覆盖了肿瘤的侵袭区域。因此，制备了含有阿霉素（ADR）的新型热敏脂质体，在40℃及以上释放其含量，经测试，该新型热敏脂质体的ADR急剧释放。计划中，高浓度的 ADR 集中在大鼠脑肿瘤（> 42 ℃）和对应于肿瘤侵袭区（42 - 40 ℃）的周围脑组织中。这些结果表明，这一新程序 1) 有助于选择性和更广泛地递送抗肿瘤药物：到达肿瘤核心，也到达肿瘤侵袭区，2）在较低温度的肿瘤侵袭区中显示正常脑组织没有热损伤，3）允许ADR和其他无论BBB问题如何，都应使用抗肿瘤药物，4）有助于抗肿瘤药物和热疗的协同作用，这种新的脂质体疗法可在临床上用作恶性胶质瘤的优越靶向化疗热疗法。