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Modification of the surface of superparamagnetic iron oxide nanoparticles to enable their safe application in humans

Authors Strehl C, Maurizi L, Gaber T, Hoff P, Broschard T, Poole AR, Hofmann H, Buttgereit F

Received 14 April 2016

Accepted for publication 24 June 2016

Published 8 November 2016 Volume 2016:11 Pages 5883—5896


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Thomas Webster

Cindy Strehl,1,2 Lionel Maurizi,3 Timo Gaber,1,2 Paula Hoff,1,2 Thomas Broschard,4 A Robin Poole,5 Heinrich Hofmann,3 Frank Buttgereit1,2

1Department of Rheumatology and Clinical Immunology, Charité – Universitätsmedizin Berlin, Berlin, Germany; 2German Rheumatism Research Centre (DRFZ), Berlin, Germany; 3Powder Technology Laboratory, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne, Switzerland; 4Non-Clinical Safety, Merck Serono, Merck KGaA, Darmstadt, Germany; 5Department of Surgery, McGill University, Montreal QC, Canada

Abstract: Combined individually tailored methods for diagnosis and therapy (theragnostics) could be beneficial in destructive diseases, such as rheumatoid arthritis. Nanoparticles are promising candidates for theragnostics due to their excellent biocompatibility. Nanoparticle modifications, such as improved surface coating, are in development to meet various requirements, although safety concerns mean that modified nanoparticles require further review before their use in medical applications is permitted. We have previously demonstrated that iron oxide nanoparticles with amino-polyvinyl alcohol (a-PVA) adsorbed on their surfaces have the unwanted effect of increasing human immune cell cytokine secretion. We hypothesized that this immune response was caused by free-floating PVA. The aim of the present study was to prevent unwanted immune reactions by further surface modification of the a-PVA nanoparticles. After cross-linking of PVA to nanoparticles to produce PVA-grafted nanoparticles, and reduction of their zeta potential, the effects on cell viability and cytokine secretion were analyzed. PVA-grafted nanoparticles still stimulated elevated cytokine secretion from human immune cells; however, this was inhibited after reduction of the zeta potential. In conclusion, covalent cross-linking of PVA to nanoparticles and adjustment of the surface charge rendered them nontoxic to immune cells, nonimmunogenic, and potentially suitable for use as theragnostic agents.

Keywords: iron oxide nanoparticles, cytokine secretion, cell viability, polyvinyl alcohol, cross-linking, surface charge

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