Antitumor activity of selective hyperthermia in tumor-bearing rats using thermosensitive magnetoliposomes as a new hyperthermic material

Abstract

The antitumor activity of dextran magnetite (DM)-incorporating thermosensitive liposomes, namely thermosensitive magnetoliposomes (TMs), as a new hyperthermic material was examined in rats bearing AH60C tumors. TMs were injected at an iron concentration of 15 mg per cm3 tumor into AH60C tumors placed subcutaneously in the backs of Donryu rats. After injection, the whole body of the rat (treated group) was exposed to a 500-kHz electromagnetic field generated by inductive heating. The treated group was further divided into once- and twice-treated groups in order to examine whether repetitive hyperthermia is possible after a single TM injection. A control group also received a TM injection but was not treated with hyperthermia. In the heated groups, there was a marked temperature rise inside the tumor up to 42°C within 7 min, but surrounding tissues were not heated. The inhibition of the growth of AH60C tumor in the treated groups was significantly greater than in the control group (P <. 01). Histological examination indicated that the tumor cells in the treated and surviving rats disappeared completely after hyperthermia and that TMs remained in the necrotic tissues. Moreover, the survival rate was significantly higher in the treated groups than in the control group (P <. 01); the twice-treated group showed even better results (100% complete recovery). Thus, selective hyperthermia with TMs may prove useful in the treatment of localized tumors.