Amiodarone is an anti-arrhythmic drug that was approved by the US Food and Drug Administration (FDA) in 1985. Pre-clinical studies suggest that Amiodarone induces cytotoxicity in several types of cancer cells, thus making it a potential candidate for use as an anti-cancer treatment. However, it is also known to cause a variety of severe side effects. We hypothesized that in addition to the cytotoxic effects observed in cancer cells Amiodarone also has an indirect effect on angiogensis, a key factor in the tumor microenvironment. In this study, we examined Amiodarone's effects on a murine tumor model comprised of U-87 MG glioblastoma multiforme (GBM) cells, known to form highly vascularized tumors. We performed several in vitro assays using tumor and endothelial cells, along with in vivo assays utilizing three murine models. Low dose Amiodarone markedly reduced the size of GBM xenograft tumors and displayed a strong anti-angiogenic effect, suggesting dual cancer fighting properties. Our findings lay the ground for further research of Amiodarone as a possible clinical agent that, used in safe doses, maintains its dual properties while averting the drug’s harmful side effects.

Background: Pre-clinical studies suggest that Amiodarone induces cytotoxicity in several types of cancer cells, thus making it a potential candidate for use as an anti-cancer treatment. In this study, we examined Amiodarone's effects on glioblastoma multiforme (GBM), a highly aggressive and hypervascularized cancer. We hypothesized that Amiodarone would show an anti-angiogenic effect on GBM in addition to its previously suggested anti-cancer activity, and that an ultra-low dose would be both effective and possibly avert the drug’s side effects. Methods: The anti-cancer activity of Amiodarone was assessed by several in vitro assays using GBM cells. This included cytotoxicity, proliferation, transwell migration, Anoikis, colony-formation and three-dimensional (3D) spheroid growth assays. The anti-angiogenic effect of Amiodarone was tested on endothelial cells, using toxicity, proliferation, migration and tube formation in vitro assays. The anti-cancer and anti-angiogenic activity of Amiodarone was examined in vivo on three different murine models. C57BL/6J mice were utilized for the corneal neovascularization model and the Matrigel plug assay. Foxn1 nu mice were inoculated with GBM cells and used for the GBM tumor xenograft model.Results: In this study, we showed that Amiodarone has a significant anti-cancer and anti-angiogenic activity in vitro. Moreover, ultra-low dose Amiodarone markedly reduced the size of GBM xenograft tumors and displayed a strong anti-angiogenic effect in vivo. Conclusions: Our results strongly suggest that Amiodarone possess dual cancer fighting properties.

Porous metals have gained interest in many fields such as biomedicine, electronics, and energy. Despite the many benefits that these structures may offer, one of the major challenges in utilizing porous metals is to incorporate active compounds, either small molecules or macromolecules, on these surfaces. Coatings that contain active molecules have previously been used for biomedical applications to enable the slow release of drugs, e.g., with drug-eluting cardiovascular stents. However, direct deposition of organic materials on metals by coatings is very difficult due to the challenge of obtaining uniform coatings, as well as issues related to layer adherence and mechanical stability. Our study describes an optimization of a production process of different porous metals, aluminum, gold, and titanium, using wet-etching. Pertinent physicochemical measurements were carried out to characterize the porous surfaces. Following the production of porous metal surface, a new methodology for incorporating active materials onto the metals by using mechanical entrapment of polymeric nanoparticles in metal pores was developed. To demonstrate our concept of active material incorporation, we produced an odor-releasing metal object with embedded particles loaded with thymol, an odoriferous molecule. Polymer particles were placed inside nanopores in a 3D-printed titanium ring. Chemical analysis, followed by smell tests, indicated that the smell intensity lasts significantly longer in the porous material containing the nanoparticles, compared with the free thymol.