Abstract 3104: Rotating magnetic beads for enhanced drug delivery: characterization of bead velocity, imaging, and adherence to cellular monolayers

Abstract

Abstract Background: Superparamagnetic iron oxide nanoparticles (SPIONs) have been touted as promising vehicles for enhancing drug delivery for cancer, stroke, and other diseases. Unfortunately, successful clinical use has been hampered by the problem of scale, since the attractive force between iron particle and magnet is inversely proportional to at least the fourth power of the intervening distance. Utilization of magnetically-induced rotary traction (MIRT) offers a way to overcome this obstacle. Here, we present initial data from the use of a new two-part system consisting of: 1) a patented rotating magnet, and 2) magnetic microbeads (MBs), which have been optimized for MIRT. Methods: MBs and the rotating magnet were provided by Pulse Therapeutics (St. Louis, MO). MBs consist of single-crystalline magnetite cores (~70 nm), which form aggregates in response to a magnetic field. Here, the field is generated by a neodymium-boron-iron permanent magnet, which is rapidly rotated causing MBs to counter-rotate (like meshed gears) at physiologic distances, and move by means of surface traction. Movement of MBs through PBS, DMEM with 5% serum, and 100% serum was measured 7.5 to 30 cm from the magnet. Suspensions of the particles were imaged at different concentrations by MRI and CT scan. 3 cancer cell lines (U87, E297, LKB1-KO), and normal vascular endothelial cells, were maintained using standard tissue culture technique. For adhesion studies, cells were grown in 6-well plates to confluence, treated with 10 uL MBs for 30 min., washed with PBS, imaged with standard light microscopy, digitized, then analyzed using Image J. Results: In our experiments, MBs moved readily through PBS, DMEM and serum at distances from 7.5 - 30 cm; with a maximum velocity at 22.5 cm (0.45 +/- 0.04 cm/sec, for serum). While MR imaging produced significant artifact as expected, MBs were clearly seen by CT scan. Adhesion of the MBs to the cancer cell lines was markedly higher than to the endothelial cells (10.9-12.0X) and to fixed cells, used as controls. Conclusions: MBs are easily rotated and moved at physiologic distances, even through 100% serum, by means of surface traction, and can be imaged by CT scan. Adhesion of MBs to cancer cells is significantly greater than to endothelial cells. These features show that the Pulse system is an extremely promising one, for use in magnetic drug targeting in the clinical setting. Citation Format: Herbert Engelhard, Zachary Gaertner, Adam Levin, Ankit Mehta, Sean Morris, Michael Sabo, Frances Creighton. Rotating magnetic beads for enhanced drug delivery: characterization of bead velocity, imaging, and adherence to cellular monolayers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3104. doi:10.1158/1538-7445.AM2017-3104