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

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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.