title: Oxidative stress response in neural stem cells exposed to different superparamagnetic iron oxide nanoparticles.
abstract: Biocompatibility, safety, and risk assessments of superparamagnetic iron oxide nanoparticles (SPIONs) are of the highest priority in researching their application in biomedicine. One improvement in the biological properties of SPIONs may be achieved by different functionalization and surface modifications. This study aims to investigate how a different surface functionalization of SPIONs - uncoated, coated with d-mannose, or coated with poly-l-lysine - affects biocompatibility. We sought to investigate murine neural stem cells (NSCs) as important model system for regenerative medicine. To reveal the possible mechanism of toxicity of SPIONs on NSCs, levels of reactive oxygen species, intracellular glutathione, mitochondrial membrane potential, cell-membrane potential, DNA damage, and activities of SOD and GPx were examined. Even in cases where reactive oxygen species levels were significantly lowered in NSCs exposed to SPIONs, we found depleted intracellular glutathione levels, altered activities of SOD and GPx, hyperpolarization of the mitochondrial membrane, dissipated cell-membrane potential, and increased DNA damage, irrespective of the surface coating applied for SPION stabilization. Although surface coating should prevent the toxic effects of SPIONs, our results showed that all of the tested SPION types affected the NSCs similarly, indicating that mitochondrial homeostasis is their major cellular target. Despite the claimed biomedical benefits of SPIONs, the refined determination of their effects on various cellular functions presented in this work highlights the need for further safety evaluations. This investigation helps to fill the knowledge gaps on the criteria that should be considered in evaluating the biocompatibility and safety of novel nanoparticles.
authors.affiliation: School of Medicine, Croatian Institute for Brain Research, University of Zagreb, Zagreb, Croatia.
authors.forename: Igor M
authors.initials: IM
authors.lastname: Pongrac
authors.affiliation: Institute for Medical Research and Occupational Health, Zagreb, Croatia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Pavičić
authors.affiliation: Institute for Medical Research and Occupational Health, Zagreb, Croatia.
authors.forename: Mirta
authors.initials: M
authors.lastname: Milić
authors.affiliation: School of Medicine, Croatian Institute for Brain Research, University of Zagreb, Zagreb, Croatia.
authors.forename: Lada
authors.initials: L
authors.lastname: Brkić Ahmed
authors.affiliation: Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Babič
authors.affiliation: Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Daniel
authors.initials: D
authors.lastname: Horák
authors.affiliation: Institute for Medical Research and Occupational Health, Zagreb, Croatia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Vinković Vrček
authors.affiliation: School of Medicine, Croatian Institute for Brain Research, University of Zagreb, Zagreb, Croatia.
authors.forename: Srećko
authors.initials: S
authors.lastname: Gajović
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D003911:Dextrans / Q000494:pharmacology*; D005290:Ferric Compounds / Q000494:pharmacology*; D057446:Hydrodynamics; D058185:Magnetite Nanoparticles; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D058953:Neural Stem Cells / Q000187:drug effects / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D055672:Static Electricity
chemical_list: D000975:Antioxidants; D003911:Dextrans; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; D017382:Reactive Oxygen Species; C000499:ferric oxide; C065507:ferumoxides
keywords: biocompatibility; genotoxicity; murine neural stem cells; oxidative stress; superparamagnetic iron oxide nanoparticles