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

恶性胶质瘤核心周围已有肿瘤细胞(肿瘤侵袭区)浸润，一般不能切除，导致肿瘤再生长，预后不良。然而，到目前为止，很少有人尝试集中治疗这个肿瘤侵袭区。我们开发了一种新的靶向化疗热疗，聚焦于肿瘤核心，也聚焦于肿瘤侵袭区。温敏性脂质体是一种微小的囊泡，可以含有药物，并在高温下有效地释放它们。我们的热疗，在42-43℃以上，可以治疗人类恶性胶质瘤的整个肿瘤核心，进行直接热杀。当加热时，40℃区域延伸到很宽的部分，覆盖了肿瘤侵袭区。为此，研制了一种新型的阿霉素温敏脂质体，其释放度在40℃以上。因此，这种新型温敏脂质体按计划迅速释放阿霉素，并在大鼠脑瘤(&gt；42℃)和与肿瘤侵袭区相对应的周围脑组织(42-40℃)中聚集了高浓度的阿霉素。这些结果表明，这一新程序有助于选择性和更广泛地将抗肿瘤药物输送到肿瘤核心和肿瘤侵袭区，2)在较低温度的肿瘤侵袭区没有显示正常脑组织的热损伤，3)允许ADR和其他抗肿瘤药物的使用而不考虑血脑屏障问题，4)有助于抗肿瘤药物和热疗的协同作用。这种新的脂质体疗法可以作为恶性胶质瘤的一种更好的靶向化疗热疗。

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.