Abstract 727: Specific destruction of iron oxide labeled cancer cells by variable gradient magnetic field.
Authors: Hapuarachchige Sudath , Kato Yoshinori , Artemov Dmitri 
Published: August 2014

Abstract
Minimally invasive cancer therapy with nanostructures such as hyperthermia treatment with superparamagnetic iron oxide (SPIO) nanoparticles that has been recently demonstrated, represents novel highly important strategy for cancer management. In this study we have demonstrated that oscillating gradients of magnetic field induce significant non-thermal damage to cells labeled with magnetic SPIO nanoparticles. Iron oxide labeling was achieved either by specific cell surface labeling with biotinylated trastuzumab antibody followed by streptavidin-conjugated SPIO nanoparticles (MiltenyiBiotec) at 4 °C to prevent internalization, or by internalization of BNF-starch nanoparticles (Micromod Partikeltechnologie) using standard cell transfection reagents. Both protocols resulted in an efficient cell labeling with SPIO confirmed by Prussian blue staining. The novel treatment procedure, called GIFT (gradient-induced Fe therapy), was implemented on a small animal Bruker Biospec 9.4T MRI scanner equipped with G060 gradient system. SPIO nanoparticles can also serve as MRI contrast agent thus enabling image-guided delivery of therapy. Cell samples or mice were positioned in the center of the gradient system of the magnet, and cycling gradients with the amplitude of Gmax = 93.5 G/cm were applied for variable periods of time. The sample temperature was stabilized by a home-built temperature controlled chamber. The treatment resulted in an efficient destruction of both surface labeled and SPIO loaded human breast cancer HER2/neu positive BT-474 cells. We also obtained preliminary results for in vivo GIFT therapy with human breast cancer MDA-MB-231/luc models expressing firefly luciferase. Cancer cells prelabeled with BNF nanoparticles were inoculated orthotopically and GIFT and T2 MR imaging were initiated starting from 48h after the tumor inoculation. The tumor viability following the treatment was longitudinally evaluated by bioluminescence imaging (BLI) and by histological endpoints. GIFT therapy resulted in significant reduction of BLI intensities from SPIO prelabeled tumors, whereas no effect was observed for unlabeled tumors or when no gradients were applied. We hypothesize that variable gradients induce structural damage to iron-oxide labeled cells in the presence of strong polarizing magnetic field and that the potential mechanism may include mechanical destruction of cell membranes and/or organelles by magnetically polarized nanoparticles or their aggregates and is not related to hyperthermia induced by the radiofrequency. GIFT can be implemented on a standard MRI system that makes the technology applicable for clinical use.
Citation Format: Sudath Hapuarachchige, Yoshinori Kato, Dmitri Artemov. Specific destruction of iron oxide labeled cancer cells by variable gradient magnetic field. [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 727. doi:10.1158/1538-7445.AM2013-727