Mechanisms of Nanoparticle Toxicity

Singh, Ashok K.

doi:10.1016/b978-0-12-801406-6.00007-8

Cited by 16 publications

(13 citation statements)

References 340 publications

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“…Properties of nanomaterials may differ from bulk material, because of their small size, large surface area and polydispersity. Compared to bulk particles with <1% of total atoms on the surface, >80% of total atoms are on the surface of nanoparticles (NPs), offering new biological properties ( Singh, 2016 ). Thus, the surface atoms will influence particle properties and size, and lead to shape-dependent physicochemical properties ( Singh, 2016 ).…”

Section: Nanotechnology and Chitosanmentioning

confidence: 99%

The Potential of Chitosan in Nanomedicine: An Overview of the Cytotoxicity of Chitosan Based Nanoparticles

et al. 2022

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The unique properties and applications of nanotechnology in targeting drug delivery, cosmetics, fabrics, water treatment and food packaging have received increased focus the last two decades. The application of nanoparticles in medicine is rapidly evolving, requiring careful investigation of toxicity before clinical use. Chitosan, a derivative of the natural polysaccharide chitin, has become increasingly relevant in modern medicine because of its unique properties as a nanoparticle. Chitosan is already widely used as a food additive and in food packaging, bandages and wound dressings. Thus, with an increasing application worldwide, cytotoxicity assessment of nanoparticles prepared from chitosan is of great interest. The purpose of this review is to provide an updated status of cytotoxicity studies scrutinizing the safety of chitosan nanoparticles used in biomedical research. A search in Ovid Medline from 23 March 1998 to 4 January 2022, with the combination of the search words Chitosan or chitosan, nanoparticle or nano particle or nanosphere or nanocapsule or nano capsule, toxicology or toxic or cytotoxic and mucosa or mucous membrane resulted in a total of 88 articles. After reviewing all the articles, those involving non-organic nanoparticles and cytotoxicity assays conducted exclusively on nanoparticles with anti-tumor effect (i.e., having cytotoxic effect) were excluded, resulting in 70 articles. Overall, the chitosan nanoparticles included in this review seem to express low cytotoxicity regardless of particle composition or cytotoxicity assay and cell line used for testing. Nonetheless, all new chitosan derivatives and compositions are recommended to undergo careful characterization and cytotoxicity assessment before being implemented on the market.

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Section: Nanotechnology and Chitosanmentioning

confidence: 99%

The Potential of Chitosan in Nanomedicine: An Overview of the Cytotoxicity of Chitosan Based Nanoparticles

et al. 2022

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“…As some ROS can be harmful to living organisms, this needs to be considered in nanotoxicological assessments. Since ROS production by NPs has been shown to activate major pathways that results in DNA damage, cytotoxicity and the development of several diseases, ,− the intrinsic ROS production needs to be evaluated both intra- and acellularly. ROS can be generated in several different ways within cells upon exposure to metal NPs.…”

Section: Introductionmentioning

confidence: 99%

Adsorption of Horseradish Peroxidase on Metallic Nanoparticles: Effects on Reactive Oxygen Species Detection Using 2′,7′-Dichlorofluorescin Diacetate

Kessler

Hedberg

McCarrick

et al. 2021

Chem. Res. Toxicol.

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The fluorescent probe 2′,7′-dichlorofluorescein diacetate (DCFH-DA) together with the enzyme horseradish peroxidase (HRP) is widely used in nanotoxicology to study acellular reactive oxygen species (ROS) production from nanoparticles (NPs). This study examined whether HRP adsorbs onto NPs of Mn, Ni, and Cu and if this surface process influences the extent of metal release and hence the ROS production measurements using the DCFH assay in phosphate buffered saline (PBS), saline, or Dulbecco’s modified Eagle’s medium (DMEM). Adsorption of HRP was evident onto all NPs and conditions, except for Mn NPs in PBS. The presence of HRP resulted in an increased release of copper from the Cu NPs in PBS and reduced levels of nickel from the Ni NPs in saline. Both metal ions in solution and the adsorption of HRP onto the NPs can change the activity of HRP and thus influence the ROS results. The effect of HRP on the NP reactivity was shown to be solution chemistry dependent. Most notable was the evident affinity/adsorption of phosphate toward the metal NPs, followed by a reduced adsorption of HRP, the concomitant reduction in released manganese from the Mn NPs, and increased levels of released metals from the Cu NPs in PBS. Minor effects were observed for the Ni NPs. The solution pH should be monitored since the release of metals can change the solution pH and the activity of HRP is known to be pH-dependent. It is furthermore essential that solution pH adjustments are made following the addition of NaOH during diacetyl removal of DCFH-DA. Even though not observed for the given exposure conditions of this study, released metal ions could possibly induce agglomeration or partial denaturation of HRP, which in turn could result in steric hindrance for H 2 O 2 to reach the active site of HRP. This study further emphasizes the influence of HRP on the background kinetics, its solution dependence, and effects on measured ROS signals. Different ways of correcting for the background are highlighted, as this can result in different interpretations of generated results. The results show that adsorption of HRP onto the metal NPs influenced the extent of metal release and may, depending on the investigated system, result in either under- or overestimated ROS signals if used together with the DCFH assay. HRP should hence be used with caution when measuring ROS in the presence of reactive metallic NPs.

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“…The exponential increase in production of engineered nanomaterials (ENMs, i.e., particles and fibers in which at least one dimension is <100 nm) in the last decade has raised concerns about their impact on human and environmental health. − While studies in a number of model species have demonstrated that ENMs induce toxicity at the phenotype level, and the molecular and cellular mechanisms that lead to ENM-induced toxicity are not yet well understood. − …”

Section: Introductionmentioning

confidence: 99%

Common Gene Expression Patterns in Environmental Model Organisms Exposed to Engineered Nanomaterials: A Meta-Analysis

Burkard

Betz

Schirmer

et al. 2019

Environ. Sci. Technol.

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The use of omics is gaining importance in the field of nanoecotoxicology; an increasing number of studies are aiming to investigate the effects and modes of action of engineered nanomaterials (ENMs) in this way. However, a systematic synthesis of the outcome of such studies regarding common responses and toxicity pathways is currently lacking. We developed an R-scripted computational pipeline to perform reanalysis and functional analysis of relevant transcriptomic data sets using a common approach, independent from the ENM type, and across different organisms, including Arabidopsis thaliana, Caenorhabditis elegans, and Danio rerio. Using the pipeline that can semiautomatically process data from different microarray technologies, we were able to determine the most common molecular mechanisms of nanotoxicity across extremely variable data sets. As expected, we found known mechanisms, such as interference with energy generation, oxidative stress, disruption of DNA synthesis, and activation of DNA-repair but also discovered that some less-described molecular responses to ENMs, such as DNA/RNA methylation, protein folding, and interference with neurological functions, are present across the different studies. Results were visualized in radar charts to assess toxicological response patterns allowing the comparison of different organisms and ENM types. This can be helpful to retrieve ENM-related hazard information and thus fill knowledge gaps in a comprehensive way in regard to the molecular underpinnings and mechanistic understanding of nanotoxicity.

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Mechanisms of Nanoparticle Toxicity

Cited by 16 publications

References 340 publications

The Potential of Chitosan in Nanomedicine: An Overview of the Cytotoxicity of Chitosan Based Nanoparticles

The Potential of Chitosan in Nanomedicine: An Overview of the Cytotoxicity of Chitosan Based Nanoparticles

Adsorption of Horseradish Peroxidase on Metallic Nanoparticles: Effects on Reactive Oxygen Species Detection Using 2′,7′-Dichlorofluorescin Diacetate

Common Gene Expression Patterns in Environmental Model Organisms Exposed to Engineered Nanomaterials: A Meta-Analysis

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