Size-dependent cytotoxicity of silver nanoparticles in human lung cells: the role of cellular uptake, agglomeration and Ag release
By A. Gliga, Sara Skoglund, I. Odnevall Wallinder, Bengt Fadeel, H. Karlsson. Particle and Fibre Toxicology, 2014
1,006 citations recorded by the source corpus.
Silver nanoparticles (AgNPs) are currently one of the most manufactured nanomaterials. A wide range of toxicity studies have been performed on various AgNPs, but these studies report a high variation in toxicity and often lack proper particle characterization. The aim of this study was to investigate size- and coating-dependent toxicity of thoroughly characterized AgNPs following exposure of human lung cells and to explore the mechanisms of toxicity. BEAS-2B cells were exposed to citrate coated AgNPs of different primary particle sizes (10, 40 and 75 nm) as well as to 10 nm PVP coated and 50 nm uncoated AgNPs. The particle agglomeration in cell medium was investigated by photon cross correlation spectroscopy (PCCS); cell viability by LDH and Alamar Blue assay; ROS induction by DCFH-DA assay; genotoxicity by alkaline comet assay and γH2AX foci formation; uptake and intracellular localization by transmission electron microscopy (TEM); and cellular dose as well as Ag release by atomic absorption spectroscopy (AAS). The results showed cytotoxicity only of the 10 nm particles independent of surface coating. In contrast, all AgNPs tested caused an increase in overall DNA damage after 24 h assessed by the comet assay, suggesting independent mechanisms for cytotoxicity and DNA damage. However, there was no γH2AX foci formation and no increased production of intracellular reactive oxygen species (ROS). The reasons for the higher toxicity of the 10 nm particles were explored by investigating particle agglomeration in cell medium, cellular uptake, intracellular localization and Ag release. Despite different agglomeration patterns, there was no evident difference in the uptake or intracellular localization of the citrate and PVP coated AgNPs. However, the 10 nm particles released significantly more Ag compared with all other AgNPs (approx. 24 wt% vs. 4–7 wt%) following 24 h in cell medium. The released fraction in cell medium did not induce any cytotoxicity, thus implying that intracellular Ag release was responsible for the toxicity. This study shows that small AgNPs (10 nm) are cytotoxic for human lung cells and that the toxicity observed is associated with the rate of intracellular Ag release, a ‘Trojan horse’ effect.
Subfields: Biomaterials, Materials Chemistry, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/f4cff5286bfcebed0f3899768daa820007ed0444
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Biomaterials
In Materials Chemistry
Citations in the corpus
- A review on biosynthesis of silver nanoparticles and their biocidal properties (2018, background): “[262] have suggested that silver ions from AgCl are released in the biological fluid and complexed.”
- Biomedical Applications of Silver Nanoparticles: An Up-to-Date Overview (2018, background): “According to recent data, the main in vitro outcomes occurring upon exposure to AgNPs were reported as increases in oxidative stress, genotoxicity, and apoptosis levels [250 – 252].”
- A review of the use of engineered nanomaterials to suppress plant disease and enhance crop yield (2015, background): “Although NP Ag toxicity to humans is an area of active research, DNA and cell membrane damage from exposure have been noted (AshaRani et al. 2009; Gliga et al. 2014; Vrček et al. 2014).”
- A systematic review on silver nanoparticles-induced cytotoxicity: Physicochemical properties and perspectives (2017, neutral): “The cytotoxicity of Ag-NPs is influenced by the variation in particle size [61].”
- Bactericidal and Cytotoxic Properties of Silver Nanoparticles (2019, methodology): “Similarly, Kim et al. demonstrated that Ag-NPs induced a significant increase in the ROS level and oxidative DNA damage in the BEAS-2B cells [202].”
- Silver Nanoparticles and Their Antibacterial Applications (2021, background): “[85] investigated the toxicity induced by AgNPs of different sizes (10, 40, and 75 nm) and with different coatings (citrate and PVP).”
- In vitro approaches to assess the hazard of nanomaterials (2017, methodology): “It has been noted that the type of NM protein corona, generated as a consequence of a specific test medium, can strongly influence the uptake and toxicity of individual NMs such that the in vitro results may be test system-specific (Gliga et al., 2014; Kim et al., 2014; Docter et al., 2015).”