Self-regulating hyperthermia induced using thermosensitive ferromagnetic material

多年来，热疗一直被用于治疗各种恶性肿瘤。居里温度(T_C)是磁性材料失去其磁性的一个转折点，在该点上会导致电流停止，从而产生热。由于热敏材料的自我调节特性，这种热敏材料能够在整个肿瘤范围内实现自动温度控制。我们开发了一种磁感应加温方法，使用足够低的TC(43℃)的热敏铁磁性颗粒来调节自动温度控制。将B16黑色素瘤细胞皮下注射到C57BL/6小鼠的背部，然后允许肿瘤生长到5 mm。然后将FMPs注射到肿瘤内，将小鼠分为3组：I组(不加温；对照组)、II组(1次加温治疗)和III组(每周2次加温，持续4周)。当暴露在磁场中时，FMPs的产热率急剧上升，在7min内达到组织中的Tc值，之后组织温度稳定在Tc值附近。在第I组和第II组，所有小鼠在30至45天内死亡。而在III组，10只小鼠中有6只在治疗120天后仍存活。我们的研究结果表明，由低T_c的FMPs介导的磁感应自我调节热疗重复治疗是一种有效的抑制黑色素瘤生长的方法。这种热疗系统的一个关键优势是它是微创的，只需一次注射即可进行自动温度控制的重复治疗。

Hyperthermia has been used for many years to treat variety of malignant tumors. The Curie temperature (Tc) is a transition point at which magnetic materials lose of its magnetic properties, which causes 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℃) 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 5mm 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 7min, after which the tissue temperature stabilized at around the Tc. In groups-I and II, all mice died within 30 to 45days. In group-III, however, 6 of 10 mice remained alive 120days 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.