Functionalized superparamagnetic iron oxide nanoparticles provide highly efficient iron-labeling in macrophages for magnetic resonance–based detection in vivo

Sharkey, J. et al. (2017) Functionalized superparamagnetic iron oxide nanoparticles provide highly efficient iron-labeling in macrophages for magnetic resonance–based detection in vivo. Cytotherapy, 19(4), pp. 555-569. (doi:10.1016/j.jcyt.2017.01.003) (PMID:28214127) (PMCID:PMC5357746)

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Abstract

Background aims: Tracking cells during regenerative cytotherapy is crucial for monitoring their safety and efficacy. Macrophages are an emerging cell-based regenerative therapy for liver disease and can be readily labeled for medical imaging. A reliable, clinically applicable cell-tracking agent would be a powerful tool to study cell biodistribution. Methods: Using a recently described chemical design, we set out to functionalize, optimize and characterize a new set of superparamagnetic iron oxide nanoparticles (SPIONs) to efficiently label macrophages for magnetic resonance imaging–based cell tracking in vivo. Results: A series of cell health and iron uptake assays determined that positively charged SPIONs (+16.8 mV) could safely label macrophages more efficiently than the formerly approved ferumoxide (−6.7 mV; Endorem) and at least 10 times more efficiently than the clinically approved SPION ferumoxytol (−24.2 mV; Rienso). An optimal labeling time of 4 h at 25 µg/mL was demonstrated to label macrophages of mouse and human origin without any adverse effects on cell viability whilst providing substantial iron uptake (>5 pg Fe/cell) that was retained for 7 days in vitro. SPION labeling caused no significant reduction in phagocytic activity and a shift toward a reversible M1-like phenotype in bone marrow–derived macrophages (BMDMs). Finally, we show that SPION-labeled BMDMs delivered via the hepatic portal vein to mice are localized in the hepatic parenchyma resulting in a 50% drop in T2* in the liver. Engraftment of exogenous cells was confirmed via immunohistochemistry up to 3 weeks posttransplantation. Discussion: A positively charged dextran-coated SPION is a promising tool to noninvasively track hepatic macrophage localization for therapeutic monitoring.

Item Type:Articles
Additional Information:This work was supported by the UK Regenerative Medicine Platform Safety and Efficacy Hub (grant ref MR/K026739/1).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Adams, Dave
Authors: Sharkey, J., Starkey Lewis, P. J., Barrow, M., Alwahsh, S. M., Noble, J., Livingstone, E., Lennen, R. J., Jansen, M. A., Carrion, J. G., Liptrott, N., Forbes, S., Adams, D. J., Chadwick, A. E., Forbes, S. J., Murray, P., Rosseinsky, M. J., Goldring, C. E., and Park, B. K.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:Cytotherapy
Publisher:Elsevier
ISSN:14653249
ISSN (Online):1477-2566
Published Online:15 February 2017

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
765131UKRMP Safety HubDave AdamsMedical Research Council (MRC)MR/K026739/1SCHOOL OF CHEMISTRY