MEDU-45. DEVELOPMENT OF A NEW ETOPOSIDE-BOUND MAGNETIC NANOPARTICLE DESIGNED TO TREAT MEDULLOBLASTOMA CELLS DISSEMINATED WITHIN CEREBROSPINAL FLUID PATHWAYS. (23rd April 2019)

• Record Type: Journal Article
• Authors: Kwasnicki, Amanda; Lakka, Sajani; Willis, Alexander; Karumudi, Bhargava; Lee, George; Liu, Bing; Hwang, Sangyeul; Esfahani, Darian; Liu, Ying; Engelhard, Herbert
• Is Part Of: Neuro-oncology. Volume 21(2019)Supplement 2
• Page Start: ii113
• Page End: ii113
• Publication Date: 2019-04-23
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noz036.203
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: BACKGROUND: Medulloblastoma cells notoriously disseminate within CSF pathways. Magnetic nanoparticles (MNPs) have potential for enhancing delivery of chemotherapy to these cells. Successful clinical use of MNPs within CSF has been hampered due to limited capacity for targeting at human-sized distances, and choice of therapeutic component. Here, we present data related to the creation and in vitro use of an MNP system containing: 1) AuFe base particles having streptavidin binding sites, and 2) biotinylated etoposide. Etoposide was chosen due to its previous use in the spinal subarachnoid space, and ease of biotinylation. Aggregates of MNPs were moved by a rotating magnet, with "surface walking" even at 10-15cm. METHODS: Etoposide-MNPs were characterized by electron microscopy, UV-vis spectroscopy, and dynamic light scattering (DLS). The rotating magnet was provided by Pulse Therapeutics. Cultured D283 cells were seeded into standard multiwell plates, and custom-made trays designed to measure translational motion. Videography was used to determine particle velocity. Cellular responses to etoposide-MNPs (vs. controls) were studied by light microscopy and MTT assay. RESULTS: Etoposide was successfully bound to base particles through the streptavidin-biotin interaction. 1 - 100uM etoposide was used. DLS showed the diameter of etoposide-MNPs to be 218+/-72nm. Etoposide-MNPs could be moved remotely by the rotating magnet, which produced a tangential velocity of 0.12+/-0.002cm/sec at 8-7cm. With 2 hours of treatment, 5uM etoposide-MNPs caused morphologic changes, and decreased D283 viability to 0.76+/-0.01% of controls. CONCLUSIONS: These data demonstrate that the novel etoposide-MNPs have cytotoxic effect, and can be targeted at physiologic distances. While further studies are underway, etoposide-MNPs, may ultimately prove useful for magnetic targeting within CSF pathways, after introduction via lumbar puncture or Ommaya reservoir. An improved ability to eradicate malignant cells within CSF would be a major step forward in the treatment of patients with disseminated medulloblastoma.