Oxidative stress response in neural stem cells exposed to different superparamagnetic iron oxide nanoparticles

Scientific paper - Original scientific paper

• Author: Ivana Vinković Vrček
• Author: Igor M. Pongrac
• Author: Ivan Pavičić
• Author: Mirta Milić
• Author: Lada Brkić Ahmed
• Author: Michal Babič
• Author: Daniel Horák
• Author: Srećko Gajović
• Author's institution: University of Zagreb; School of Medicine
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences

Abstract (english)

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.

• Keywords (english): Animals; Antioxidants/pharmacology; Cell Survival/drug effects; DNA Damage; Dextrans/pharmacology; Ferric Compounds/pharmacology; Hydrodynamics; Magnetite Nanoparticles; Membrane Potential, Mitochondrial/drug effects; Membrane Potentials/drug effects; Mice, Inbred C57BL; Nanoparticles/chemistry; Nanoparticles/ultrastructure; Neural Stem Cells/drug effects; Neural Stem Cells/pathology; Oxidative Stress/drug effects; Reactive Oxygen Species/metabolism; Static Electricity
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Accepted version
• Journal title: International Journal of Nanomedicine
• Numbering: vol. 11, pp. 1701-1715
• p-ISSN: 1178-2013
• DOI: https://doi.org/10.2147/IJN.S102730
• URN:NBN: urn:nbn:hr:105:932543
• Publication: 2016-04-26
• Document URL: https://doi.org/10.2147/IJN.S102730
• Type of resource: Text
• Access conditions: Open access
• Created on: 2024-03-28 08:50:20