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

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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 .