Journal article
Silica nanoparticle-generated ROS as a predictor of cellular toxicity: mechanistic insights and safety by design
Environmental science. Nano, Vol.3(1), pp.56-66
2016
DOI: 10.1039/C5EN00179J
PMCID: PMC4795909
PMID: 26998307
Abstract
Evaluating toxicological responses of engineered nanomaterials such as silica nanoparticles is critical in assessing health risks and exposure limits. Biological assays can be used to evaluate cytotoxicity of individual materials, but specific nano-bio interactions—which govern its physiological response—cannot currently be predicted from materials characterization and physicochemical properties. Understanding the role of free radical generation from nanomaterial surfaces facilitates understanding of a potential toxicity mechanism and provides insight into how toxic effects can be assessed. Size-matched mesoporous and nonporous silica nanoparticles in aminopropyl-functionalized and native forms were investigated to analyze the effects of porosity and surface functionalization on the observed cytotoxicity. In vitro cell viability data in a murine macrophage cell line (RAW 264.7) provides a model for what might be observed in terms of cellular toxicity upon an environmental or industrial exposure to silica nanoparticles. Electron paramagnetic resonance spectroscopy was implemented to study free radical species generated from the surface of these nanomaterials and the signal intensity was correlated with cellular toxicity. In addition, in vitro assay of intracellular reactive oxygen species (ROS) matched well with both the EPR and cell viability data. Overall, spectroscopic and in vitro studies correlate well and implicate production of ROS from a surface-catalyzed reaction as a predictor of cellular toxicity. The data demonstrate that mesoporous materials are intrinsically less toxic than nonporous materials, and that surface functionalization can mitigate toxicity in nonporous materials by reducing free radical production. The broader implications are in terms of safety by design of nanomaterials, which can only be extracted by mechanistic studies such as the ones reported here.
Details
- Title: Subtitle
- Silica nanoparticle-generated ROS as a predictor of cellular toxicity: mechanistic insights and safety by design
- Creators
- Sean E Lehman - Department of Chemistry, University of Iowa, Iowa City, USAAngie S Morris - Department of Chemistry, University of Iowa, Iowa City, USA, Division of Pharmaceutics and Translational TherapeuticsPaul S Mueller - Department of Chemistry, University of Iowa, Iowa City, USAAliasger K Salem - Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, USAVicki H Grassian - Department of Chemistry, University of Iowa, Iowa City, USASarah C Larsen - Department of Chemistry, University of Iowa, Iowa City, USA
- Resource Type
- Journal article
- Publication Details
- Environmental science. Nano, Vol.3(1), pp.56-66
- DOI
- 10.1039/C5EN00179J
- PMID
- 26998307
- PMCID
- PMC4795909
- NLM abbreviation
- Environ Sci Nano
- ISSN
- 2051-8153
- eISSN
- 2051-8161
- Grant note
- DOI: 10.13039/100000066, name: National Institute of Environmental Health Sciences, award: P30 ES05605; DOI: 10.13039/100000002, name: National Institutes of Health, award: P30CA086862; DOI: 10.13039/100000072, name: National Institute of Dental and Craniofacial Research, award: NRSA T90
- Language
- English
- Date published
- 2016
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Chemistry; Dental Research; Chemical and Biochemical Engineering
- Record Identifier
- 9984216701102771
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