Self-regulating hyperthermia induced using thermosensitive ferromagnetic material with a low Curie temperature.

ABSTRACT

Hyperthermia has been used for many years to treat a variety of malignant tumors. The Curie temperature (Tc) is a transition point at which magnetic materials lose their magnetic properties, causing a cessation of current and thus heat production. The Tc enables automatic temperature control throughout a tumor as a result of the self-regulating nature of the thermosensitive material. We have developed a method of magnetically-induced hyperthermia using thermosensitive ferromagnetic particles (FMPs) with low Tc (43 degrees C), enough to mediate automatic temperature control. B16 melanoma cells were subcutaneously injected into the backs of C57BL/6 mice, after which tumors were allowed to grow to 5 mm in diameter. FMPs were then injected into the tumors, and the mice were divided into three groups group I (no hyperthermia, control); group II (one hyperthermia treatment); and group III (hyperthermia twice a week for 4 weeks). When exposed to a magnetic field, the FMPs showed a sharp rise in heat production, reaching the Tc in tissue within 7 min, after which the tissue temperature stabilized at approximately the Tc. In groups I and II, all mice died within 30-45 days. In group III, however, 6 of 10 mice remained alive 120 days after beginning treatment. Our findings suggest that repeated treatment with magnetically-induced self-regulating hyperthermia, mediated by FMPs with a low Tc, is an effective means of suppressing melanoma growth. A key advantage of this hyperthermia system is that it is minimally invasive, requiring only a single injection for repeated treatments with automatic temperature control.