title: Anti-oxidative effects and harmlessness of asymmetric Au@Fe₃O₄ Janus particles on human blood cells.
abstract: The physical properties of asymmetric Janus particles are highly promising for future biomedical applications. However, only a few data is available on their biological impact on human cells. We investigated the biological impact of different Au@Fe3O4 Janus particle formulations in vitro to analyse specific uptake modalities and their potential cytotoxic effects on human cells of the blood regarding intravenous injection. We demonstrate that Au@Fe3O4 Janus particles exhibit a similar or even better biocompatibility compared to the well-studied spherical iron oxide nanoparticles. The impact of Janus particles on cells depends mainly on three factors. (1) Surface functionalization: NH2-functionalization of the Au or iron oxide domain induces a pronounced reduction of cell viability in contrast to non-functionalized variants which is caused by the damage of intracellular membranes. (2) The nature of the metal oxide component, greatly affects cell viability, as shown by a comparison with Au@MnO Janus particles. (3) The overall surface charge and the size of nanoparticles have a higher impact on internalization and cellular metabolism than the Janus character per se. Interestingly, Janus particle associated DNA damage is independent of the effects on the cellular ATP level. However, not only the structure and functionalization of the Janus particle surface determines the particle's adhesion and intracellular fate, but also the constitution of the cell surface as shown by different modification experiments. The multifactorial in vitro approach presented in this study demonstrated the high capability of the Janus particles. Especially Au@Fe3O4 Janus particles bear great potential for applications in vivo.
authors.affiliation: Department of Experimental Radiology, Institute of Diagnostic and Interventional Radiology I, Jena University Hospital, Friedrich Schiller University Jena, Forschungszentrum Lobeda, Erlanger Allee 101, D-07747 Jena, Germany. Electronic address: lisa.landgraf@med.uni-jena.de.
authors.forename: Lisa
authors.initials: L
authors.lastname: Landgraf
authors.affiliation: Department of Experimental Radiology, Institute of Diagnostic and Interventional Radiology I, Jena University Hospital, Friedrich Schiller University Jena, Forschungszentrum Lobeda, Erlanger Allee 101, D-07747 Jena, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Ernst
authors.affiliation: Johannes Gutenberg-Universität, Institut für Anorganische Chemie und Analytische Chemie, Duesbergweg 10-14, D-55128 Mainz, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Schick
authors.affiliation: Johannes Gutenberg-Universität, Institut für Anorganische Chemie und Analytische Chemie, Duesbergweg 10-14, D-55128 Mainz, Germany.
authors.forename: Oskar
authors.initials: O
authors.lastname: Köhler
authors.affiliation: Universitätsklinikum Jena, Institut für Anatomie II, Teichgraben 7, D-07743 Jena, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Oehring
authors.affiliation: Johannes Gutenberg-Universität, Institut für Anorganische Chemie und Analytische Chemie, Duesbergweg 10-14, D-55128 Mainz, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Tremel
authors.affiliation: Department of Experimental Radiology, Institute of Diagnostic and Interventional Radiology I, Jena University Hospital, Friedrich Schiller University Jena, Forschungszentrum Lobeda, Erlanger Allee 101, D-07747 Jena, Germany. Electronic address: ingrid.hilger@med.uni-jena.de.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hilger
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D001773:Blood Cells / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D055598:Chemical Phenomena; D004249:DNA Damage / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D005290:Ferric Compounds / Q000737:chemistry / Q000494:pharmacology*; D006046:Gold / Q000737:chemistry; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D017382:Reactive Oxygen Species / Q000378:metabolism; D013499:Surface Properties
chemical_list: D000975:Antioxidants; D005290:Ferric Compounds; D017382:Reactive Oxygen Species; C000499:ferric oxide; D006046:Gold
keywords: Amino functionalization; Blood cells; Cell membrane; Cell metabolism; Janus particle; Uptake