Abstract 5568: Thermochemotherapy with controlled drug delivery using a novel magnetic anti-cancer drug .

Abstract

Abstract Background: Radical surgery for patients with oral cancer may cause dysfunction, such as dysphagia, dysarthria, or mastication disorders, leading to decreased quality of life in cancer patients. Here, we report the development of a novel magnetic anti-cancer drug, EI236, which may enable us to reduce such problems. EI236 possesses three features; anti-cancer effect alike cisplatin, controlled drug delivery using a magnet, and hyperthermic effect upon exposure to an alternating current magnetic field (ACMF). We thus examined the efficacy of EI236 in treating oral cancer in a rabbit cancer model. Methods: Cell proliferation was measured by MTT assays. We established the rabbit tongue cancer model using VX2 cells, which are readily transplantable in vivo. Electromagnet was used to attract EI236 to the site of tongue cancer by controlled drug delivery (CDR), and ACMF to generate heat from EI236 (HT). Rabbits were divided into 4 groups: control group, intravenous EI236 injection group (5mg/kg×7days) (i.v.), intravenous EI236 injection + electromagnet group (i.v. + CDR), intravenous EI236 injection + electromagnet + ACMF group (i.v. + CDR + HT). The size of tumors was measured daily for 7 days, followed by histopathological evaluation. Of note, EI236 was injected at the same dose in the three groups. Results: EI236 showed anti-cancer effects in a dose-dependent manner in VX2 cells. The IC50 value of EI236 was 7.5μM in cultured cells. The resultant tumor volume after EI236 i.v. injection treatment in rabbits was as follows; 319.3±40.0% for control, 228.5±94.3% for i.v., 91.5±27.4X% for i.v. + CDR, 24±8.2% for i.v. + CDR + HT, indicating that the i.v. + CDR + HT group showed the greatest decrease. It also showed the largest necrotic area in H-E staining analysis. The tumor cell nucleus, as determined by Ki67 staining, were mostly disappeared. Conclusion: Anti-cancer effect of EI236 was synergistically increased in the presence of CDR and/or HT. EI236 may serve as a novel anti-cancer therapy that enables CDR and HT at the same time. Citation Format: Itaru Sato, Kenji Mitsudo, Masanari Umemura, Xianfeng Feng, Hidenobu Fukumura, Haruki Eguchi, Hideyuki Nakashima, Mitomu Kioi, Iwai Tohnai, Yoshihiro Ishikawa. Thermochemotherapy with controlled drug delivery using a novel magnetic anti-cancer drug . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5568. doi:10.1158/1538-7445.AM2013-5568