title: Modification of the surface of superparamagnetic iron oxide nanoparticles to enable their safe application in humans.
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.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany; German Rheumatism Research Centre (DRFZ), Berlin, Germany.
authors.forename: Cindy
authors.initials: C
authors.lastname: Strehl
authors.affiliation: Powder Technology Laboratory, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne, Switzerland.
authors.forename: Lionel
authors.initials: L
authors.lastname: Maurizi
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany; German Rheumatism Research Centre (DRFZ), Berlin, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Gaber
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany; German Rheumatism Research Centre (DRFZ), Berlin, Germany.
authors.forename: Paula
authors.initials: P
authors.lastname: Hoff
authors.affiliation: Non-Clinical Safety, Merck Serono, Merck KGaA, Darmstadt, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Broschard
authors.affiliation: Department of Surgery, McGill University, Montreal QC, Canada.
authors.forename: A Robin
authors.initials: AR
authors.lastname: Poole
authors.affiliation: Powder Technology Laboratory, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne, Switzerland.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Hofmann
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany; German Rheumatism Research Centre (DRFZ), Berlin, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Buttgereit
mesh_terms: D000327:Adsorption; D001773:Blood Cells / Q000187:drug effects* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D005290:Ferric Compounds / Q000737:chemistry*; D005434:Flow Cytometry; D006801:Humans; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011142:Polyvinyl Alcohol / Q000737:chemistry*
chemical_list: D016207:Cytokines; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; C000499:ferric oxide; D011142:Polyvinyl Alcohol
keywords: cell viability; cross-linking; cytokine secretion; iron oxide nanoparticles; polyvinyl alcohol; surface charge