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Hyperthermia and chemotherapy using Fe(Salen) nanoparticles might impact glioblastoma treatment.

Scientific reports (2017-02-22)
Makoto Ohtake, Masanari Umemura, Itaru Sato, Taisuke Akimoto, Kayoko Oda, Akane Nagasako, Jeong-Hwan Kim, Takayuki Fujita, Utako Yokoyama, Tomohiro Nakayama, Yujiro Hoshino, Mai Ishiba, Susumu Tokura, Masakazu Hara, Tomoya Muramoto, Sotoshi Yamada, Takatsugu Masuda, Ichio Aoki, Yasushi Takemura, Hidetoshi Murata, Haruki Eguchi, Nobutaka Kawahara, Yoshihiro Ishikawa
ABSTRACT

We previously reported that μ-oxo N,N'-bis(salicylidene)ethylenediamine iron [Fe(Salen)], a magnetic organic compound, has direct anti-tumor activity, and generates heat in an alternating magnetic field (AMF). We showed that Fe(Salen) nanoparticles are useful for combined hyperthermia-chemotherapy of tongue cancer. Here, we have examined the effect of Fe(Salen) on human glioblastoma (GB). Fe(Salen) showed in vitro anti-tumor activity towards several human GB cell lines. It inhibited cell proliferation, and its apoptosis-inducing activity was greater than that of clinically used drugs. Fe(Salen) also showed in vivo anti-tumor activity in the mouse brain. We evaluated the drug distribution and systemic side effects of intracerebrally injected Fe(Salen) nanoparticles in rats. Further, to examine whether hyperthermia, which was induced by exposing Fe(Salen) nanoparticles to AMF, enhanced the intrinsic anti-tumor effect of Fe(Salen), we used a mouse model grafted with U251 cells on the left leg. Fe(Salen), BCNU, or normal saline was injected into the tumor in the presence or absence of AMF exposure. The combination of Fe(Salen) injection and AMF exposure showed a greater anti-tumor effect than did either Fe(Salen) or BCNU alone. Our results indicate that hyperthermia and chemotherapy with single-drug nanoparticles could be done for GB treatment.

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2′,7′-Dichlorofluorescein diacetate, BioReagent, suitable for fluorescence, ≥95% (HPLC)