Dextran-coated superparamagnetic iron oxide nanoparticles for magnetic resonance imaging: evaluation of size-dependent imaging properties, storage stability and safety
Received 9 November 2017
Accepted for publication 1 December 2017
Published 28 March 2018 Volume 2018:13 Pages 1899—1915
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Thomas J. Webster
Harald Unterweger,1 László Dézsi,2,3 Jasmin Matuszak,1 Christina Janko,1 Marina Poettler,1 Jutta Jordan,4 Tobias Bäuerle,4 János Szebeni,2,3 Tobias Fey,5 Aldo R Boccaccini,6 Christoph Alexiou,1 Iwona Cicha1
1ENT Department, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung Professorship, Universitätsklinikum Erlangen, Erlangen, Germany; 2Nanomedicine Research and Education Center, Institute of Pathophysiology, Semmelweis University, Budapest, Hungary; 3SeroScience Ltd., Budapest, Hungary; 4Institute of Radiology, Preclinical Imaging Platform Erlangen, Universitätsklinikum Erlangen, Erlangen, Germany; 5Institute of Glass and Ceramics, Department of Materials Science and Engineering, University Erlangen-Nuremberg, Erlangen, Germany; 6Institute of Biomaterials, Department of Materials Science and Engineering, University Erlangen-Nuremberg, Erlangen, Germany
Background: Rising criticism of currently available contrast agents for magnetic resonance imaging, either due to their side effects or limited possibilities in terms of functional imaging, evoked the need for safer and more versatile agents. We previously demonstrated the suitability of novel dextran-coated superparamagnetic iron oxide nanoparticles (SPIONDex) for biomedical applications in terms of safety and biocompatibility.
Methods: In the present study, we investigated the size-dependent cross-linking process of these particles as well as the size dependency of their imaging properties. For the latter purpose, we adopted a simple and easy-to-perform experiment to estimate the relaxivity of the particles. Furthermore, we performed an extensive analysis of the particles’ storage stability under different temperature conditions, showing their superb stability and the lack of any signs of agglomeration or sedimentation during a 12 week period.
Results: Independent of their size, SPIONDex displayed no irritation potential in a chick chorioallantoic membrane assay. Cell uptake studies of ultra-small (30 nm) SPIONDex confirmed their internalization by macrophages, but not by non-phagocytic cells. Additionally, complement activation-related pseudoallergy (CARPA) experiments in pigs treated with ultra-small SPIONDex indicated the absence of hypersensitivity reactions.
Conclusion: These results emphasize the exceptional safety of SPIONDex, setting them apart from the existing SPION-based contrast agents and making them a very promising candidate for further clinical development.
Keywords: CARPA, cross-linking, irritation potential, MRI, SPION, storage stability
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