The role of iron redox state in the genotoxicity of ultrafine superparamagnetic iron oxide nanoparticles.
Ultrafine superparamagnetic iron oxide nanoparticles (USPION) hold great potential for revolutionising biomedical applications such as MRI, localised hyperthermia, and targeted drug delivery. Though evidence is increasing regarding the influence of nanoparticle physico-chemical features on toxicity, data however, is lacking that assesses a range of such characteristics in parallel. We show that iron redox state, a subtle though important physico-chemical feature of USPION, dramatically modifies the cellular uptake of these nanoparticles and influences their induction of DNA damage. Surface chemistry was also found to have an impact and evidence to support a potential mechanism of oxidative DNA damage behind the observed responses has been demonstrated. As human exposure to ferrofluids is predicted to increase through nanomedicine based therapeutics, these findings are important in guiding the fabrication of USPION to ensure they have characteristics that support biocompatibility.
Institute of Life Science, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, Wales, UK. n.singh@swansea.ac.uk
Neenu
N
Singh
Gareth J S
GJ
Jenkins
Bryant C
BC
Nelson
Bryce J
BJ
Marquis
Thierry G G
TG
Maffeis
Andy P
AP
Brown
Paul M
PM
Williams
Chris J
CJ
Wright
Shareen H
SH
Doak
D002460:Cell Line; D004249:DNA Damage / Q000187:drug effects; D005290:Ferric Compounds / Q000009:adverse effects / Q000737:chemistry*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D058185:Magnetite Nanoparticles / Q000009:adverse effects / Q000737:chemistry* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D010084:Oxidation-Reduction; D056951:Photoelectron Spectroscopy
D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; C000499:ferric oxide