Antitumor effects of inductive hyperthermia using magnetic ferucarbotran nanoparticles on human lung cancer xenografts in nude mice

Tomoyuki Araya,¹ Kazuo Kasahara,¹ Shingo Nishikawa,¹ Hideharu Kimura,¹ Takashi Sone,¹ Hideo Nagae,² Yoshio Ikehata,³ Isamu Nagano,³ Masaki Fujimura<sup>1

1</sup>Department of Respiratory Medicine, Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, ²Cooperative Research Center for Kanazawa University, ³Department of Information and Systems Engineering, Kanazawa University, Kanazawa, Japan

Background: The effects of inductive hyperthermia on lung cancer have yet to be fully investigated. Magnetic nanoparticles used in inductive hyperthermia are made-to-order and expensive. This study was performed to investigate the use of ferucarbotran in inductive hyperthermia and to clarify whether inductive hyperthermia using ferucarbotran promotes antitumor effects in vivo using a lung cancer cell line.
Methods: We injected A549 cells subcutaneously into the right thighs of BALB/c nu/nu nude mice. Forty mice with A549 xenografts were then classified into three groups. Group 1 was the control group. All mice in groups 2 and 3 had ferucarbotran injected into their tumors, and mice in group 3 were then subjected to alternating magnetic field irradiation. We evaluated tumor temperature during the hyperthermic procedure, the time course of tumor growth, histologic findings in tumors after hyperthermic treatment, and adverse events.
Results: Intratumor temperature rose rapidly and was maintained at 43°C–45°C for 20 minutes in an alternating magnetic field. Tumor volumes in groups 1 and 2 increased exponentially, but tumor growth in group 3 was significantly suppressed. No severe adverse events were observed. Histologic findings for the tumors in group 3 revealed mainly necrosis.
Conclusion: Inductive hyperthermia using ferucarbotran is a beneficial and promising approach in the treatment of lung cancer. Ferucarbotran is a novel tool for further development of inductive hyperthermia.
Keywords: inductive hyperthermia, ferucarbotran, magnetic nanoparticles, alternating magnetic field, lung cancer, human use