Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published May 7, 2015 | Published + Supplemental Material
Journal Article Open

Functionalized iron oxide nanoparticles for controlling the movement of immune cells


Immunotherapy is currently being investigated for the treatment of many diseases, including cancer. The ability to control the location of immune cells during or following activation would represent a powerful new technique for this field. Targeted magnetic delivery is emerging as a technique for controlling cell movement and localization. Here we show that this technique can be extended to microglia, the primary phagocytic immune cells in the central nervous system. The magnetized microglia were generated by loading the cells with iron oxide nanoparticles functionalized with CpG oligonucleotides, serving as a proof of principle that nanoparticles can be used to both deliver an immunostimulatory cargo to cells and to control the movement of the cells. The nanoparticle-oligonucleotide conjugates are efficiently internalized, non-toxic, and immunostimulatory. We demonstrate that the in vitro migration of the adherent, loaded microglia can be controlled by an external magnetic field and that magnetically-induced migration is non-cytotoxic. In order to capture video of this magnetically-induced migration of loaded cells, a novel 3D-printed "cell box" was designed to facilitate our imaging application. Analysis of cell movement velocities clearly demonstrate increased cell velocities toward the magnet. These studies represent the initial step towards our final goal of using nanoparticles to both activate immune cells and to control their trafficking within the diseased brain.

Additional Information

© 2015 Royal Society of Chemistry. Received 19th August 2013; accepted 24th March 2015. We gratefully acknowledge ICP-MS instrumentation under the supervision of Nathan Dalleska at the Environmental Analysis Center at the California Institute of Technology. We thank Denise Keen from the Mass Spectrometry and Proteomics Core Facility at the Beckman Research Institute of the City of Hope for assistance with mass spectrometry. The authors gratefully acknowledge Marcia M. Miller, Zhuo Li and Ricardo Zerda for assistance with the TEM from the COH Electron Microscope Core Facility. The authors gratefully acknowledge Brian Armstrong and Tina Patel for assistance with fluorescent and bright field microscopy from the Light Microscopy Digital Imaging Core. The authors gratefully acknowledge Kaushik Dasgupta and Jeff Sherman for their dedicated assistance in magnetic manipulation of magnetized cells. The authors would like to also thank Brian Hong for proofreading this manuscript. Finally, the authors would like to thank ONR N00014-02-1 0958 for funding for the TEM, NSF DBI-9970143 for funding for the Ultramicrotome, R21NS081594, R01CA155769, R21CA189223, City of Hope-Caltech Biomedical Research Initiative, The Kenneth T. and Eileen L. Norris Foundation, STOP Cancer, and the ThinkCure! Foundation for research funding. Research reported in this publication included work performed in the Light Microscopy Digital Imaging and Electron Microscopy Cores supported by the National Cancer Institute of the National Institutes of Health under award number P30CA33572. Electronic supplementary information (ESI) available: Transmission electron microscopy images of the particles, additional independent experiments for the NFκB activity and exocytosis assays, TEM images for the SPION untreated cells, bright field microscopy images of the cells alone in the presence and absence of magnet, images of the magnetic movement experiments at higher doses of SPION, full uncropped images of the post-migration LIVE/DEAD assay, and a video file of cell movement.

Attached Files

Published - c3nr04421a.pdf

Supplemental Material - c3nr04421a1.pdf

Supplemental Material - c3nr04421a2.zip


Files (50.0 MB)
Name Size Download all
916.5 kB Preview Download
42.4 MB Preview Download
6.7 MB Preview Download

Additional details

August 20, 2023
August 20, 2023