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.

Redox-active nanomaterials for nanomedicine applications

“…However, heightened ROS levels as promoted by SPIONs are often detrimental to biological systems and impact their use in most of their designed applications. A recent study by Pongrac et al 47 monitored several oxidative stress endpoints in mouse neural stem cells (NSCs) to investigate the impact of different surface functionalizations (uncoated, D-mannose-coated, and poly-L-lysine-coated) on SPION toxicity. Due to their ability to differentiate into many types of specialized cells, stem cells are the focus of much research attention for their use in regenerative medicine therapies.…”

“…Also of note were the authors’ discussions regarding the possibility that underlying cellular functions could still be impaired despite “rough” toxicity end-points measurements (e.g., cellular viability, ROS levels) approaching their limit of detection. 47…”

PEG/Dextran Double Layer Influences Fe Ion Release and Colloidal Stability of Iron Oxide Nanoparticles

“…Commercial SPIONs generally possess a physiosorbed dextran layer around their core. Unfortunately, these nanoparticles (NPs) have demonstrated toxicity and side effects in clinical trials 7 . For instance, 23% of patients receiving Ferumoxtran-10 (a dextran coated SPION) were reported to experience side effects 8 .…”

Imaging Gliomas with Nanoparticle-Labeled Stem Cells

“…[ 30 ] Other studies on this topic have further developed the research on NSC-based drug administration,[ 31 32 ] gene therapy,[ 33 34 ] and application of the bystander effect. [ 35 36 37 ] Conversely, the incorporation of nanomedicine to NSCs has led to extensive research in this realm, including the effect of nanomaterials on NSC biology,[ 38 39 40 41 ] enhanced material loading,[ 42 43 44 45 ] stem cell tracking,[ 46 47 48 49 50 51 ] and tumor treatment. [ 32 52 ]…”