A novel etoposide-bound magnetic nanoparticle for remote targeting of cancer cells

Background: Magnetic nanoparticles (MNPs) have potential for enhancing drug delivery in selected cancer patients. To date, successful clinical use of MNPs has been limited due to the: 1) limited capacity for targeting at human-sized distances, 2) route of delivery, and 3) choice of therapeutic component. Here, we present data related to the creation and in vitro use of a new two-part MNP system consisting of: 1) an AuFe base particle having streptavidin binding sites, and 2) biotinylated etoposide, which was bound to the base particle. Etoposide was chosen in part due to its previous clinical use within cerebrospinal fluid, which could serve as a delivery medium for the new particle. Methods: Base MNPs were manufactured by IMRA America, Inc., and combined with biotinylated etoposide to create AuFe-etoposide particles (etop-MNPs), which have not been previously described. Etop-MNPs were characterized by electron microscopy, UV-vis spectroscopy, and DLS. Etop-MNPs could be moved at a distance (e.g. 10 cm) by means of a “surface walking” phenomenon, occurring in response to a rotating neodymium-boron-iron permanent magnet, kindly provided by Pulse Therapeutics (St. Louis, MO). Cell lines (including D283, U138, and normal endothelial cells) were maintained using standard tissue culture technique. Viability of the cells in response to the MNP base particles, etoposide alone, and etop-MNPs, was studied by light microscopy and MTT assay. Results: Etoposide was successfully bound to the IMRA base particle through the streptavidin-biotin interaction. Typically, 100uM etoposide was used. Etop-MNPs could be moved remotely by the rotating magnet, which produced a tangential particle velocity of 0.15 +/- 0.026 cm/sec. With 2 hours of treatment, etop-MNPs caused morphologic changes and decreased cancer cell viability to 0.50 +/- 0.03 percent that of control values. Conclusions: These findings indicate that our novel etop-MNPs have tumoricidal effect, and can be moved relatively rapidly at physiologic distances, using a rotating magnet. Etop-MNPs, may therefore prove to be useful for magnetic drug targeting in clinical settings, such as intrathecal use within the spinal subarachnoid space. Citation Format: Alexander Willis, Bhargava Karumudi, Bing Liu, Ashley Sough, Sangyeul Hwang, Ying Liu, Herbert Engelhard. A novel etoposide-bound magnetic nanoparticle for remote targeting of cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2166.