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Title: All that is silver is not toxic: silver ion and particle kinetics reveals the role of silver ion aging and dosimetry on the toxicity of silver nanoparticles

Abstract

Background When suspended in cell culture medium, nano-objects composed of soluble metals such as silver can dissolve resulting in ion formation, altered particle properties (e.g. mass, morphology, etc.), and modulated cellular dose. Cultured cells are exposed not just to nanoparticles but to a complex, dynamic mixture of altered nanoparticles, free ions, and ion-ligand complexes. Here, three different cell types (RAW 264.7 macrophages and bone marrow derived macrophages from wild-type C57BL/6J mice and Scavenger Receptor A deficient (SR-A(-/-)) mice) were exposed to 20 and 110 nm silver nanoparticles, and RAW 264.7 cells were exposed to freshly mixed silver ions, aged silver ions (ions incubated in cell culture medium), and ions formed from nanoparticle dissolution. The In Vitro Sedimentation, Diffusion, Dissolution, and Dosimetry Model (ISD3) was used to predict dose metrics for each exposure scenario. Results Silver nanoparticles, freshly mixed ions, and ions from nanoparticle dissolution were toxic, while aged ions were not toxic. Macrophages from SR-A(-/-) mice did not take up 20 nm silver nanoparticles as well as wild-types but demonstrated no differences in silver levels after exposure to 110 nm nanoparticles. Dose response modeling with ISD3 predicted dose metrics suggest that amount of ions in cells and area under themore » curve (AUC) of ion amount in cells are the most predictive of cell viability after nanoparticle and combined nanoparticle/dissolution-formed-ions exposures, respectively. Conclusions Results of this study suggest that the unbound silver cation is the ultimate toxicant, and ions formed extracellularly drive toxicity after exposure to nanoparticles. Applying computational modeling (ISD3) to better understand dose metrics for soluble nanoparticles allows for better interpretation of in vitro hazard assessments.« less

Authors:
ORCiD logo; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1489240
Report Number(s):
PNNL-SA-135829
Journal ID: ISSN 1743-8977
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
Particle and Fibre Toxicology
Additional Journal Information:
Journal Volume: 15; Journal Issue: 1; Journal ID: ISSN 1743-8977
Country of Publication:
United States
Language:
English

Citation Formats

Smith, Jordan N., Thomas, Dennis G., Jolley, Hadley, Kodali, Vamsi K., Littke, Matthew H., Munusamy, Prabhakaran, Baer, Donald R., Gaffrey, Matthew J., Thrall, Brian D., and Teeguarden, Justin G.. All that is silver is not toxic: silver ion and particle kinetics reveals the role of silver ion aging and dosimetry on the toxicity of silver nanoparticles. United States: N. p., 2018. Web. doi:10.1186/s12989-018-0283-z.
Smith, Jordan N., Thomas, Dennis G., Jolley, Hadley, Kodali, Vamsi K., Littke, Matthew H., Munusamy, Prabhakaran, Baer, Donald R., Gaffrey, Matthew J., Thrall, Brian D., & Teeguarden, Justin G.. All that is silver is not toxic: silver ion and particle kinetics reveals the role of silver ion aging and dosimetry on the toxicity of silver nanoparticles. United States. doi:10.1186/s12989-018-0283-z.
Smith, Jordan N., Thomas, Dennis G., Jolley, Hadley, Kodali, Vamsi K., Littke, Matthew H., Munusamy, Prabhakaran, Baer, Donald R., Gaffrey, Matthew J., Thrall, Brian D., and Teeguarden, Justin G.. Sat . "All that is silver is not toxic: silver ion and particle kinetics reveals the role of silver ion aging and dosimetry on the toxicity of silver nanoparticles". United States. doi:10.1186/s12989-018-0283-z.
@article{osti_1489240,
title = {All that is silver is not toxic: silver ion and particle kinetics reveals the role of silver ion aging and dosimetry on the toxicity of silver nanoparticles},
author = {Smith, Jordan N. and Thomas, Dennis G. and Jolley, Hadley and Kodali, Vamsi K. and Littke, Matthew H. and Munusamy, Prabhakaran and Baer, Donald R. and Gaffrey, Matthew J. and Thrall, Brian D. and Teeguarden, Justin G.},
abstractNote = {Background When suspended in cell culture medium, nano-objects composed of soluble metals such as silver can dissolve resulting in ion formation, altered particle properties (e.g. mass, morphology, etc.), and modulated cellular dose. Cultured cells are exposed not just to nanoparticles but to a complex, dynamic mixture of altered nanoparticles, free ions, and ion-ligand complexes. Here, three different cell types (RAW 264.7 macrophages and bone marrow derived macrophages from wild-type C57BL/6J mice and Scavenger Receptor A deficient (SR-A(-/-)) mice) were exposed to 20 and 110 nm silver nanoparticles, and RAW 264.7 cells were exposed to freshly mixed silver ions, aged silver ions (ions incubated in cell culture medium), and ions formed from nanoparticle dissolution. The In Vitro Sedimentation, Diffusion, Dissolution, and Dosimetry Model (ISD3) was used to predict dose metrics for each exposure scenario. Results Silver nanoparticles, freshly mixed ions, and ions from nanoparticle dissolution were toxic, while aged ions were not toxic. Macrophages from SR-A(-/-) mice did not take up 20 nm silver nanoparticles as well as wild-types but demonstrated no differences in silver levels after exposure to 110 nm nanoparticles. Dose response modeling with ISD3 predicted dose metrics suggest that amount of ions in cells and area under the curve (AUC) of ion amount in cells are the most predictive of cell viability after nanoparticle and combined nanoparticle/dissolution-formed-ions exposures, respectively. Conclusions Results of this study suggest that the unbound silver cation is the ultimate toxicant, and ions formed extracellularly drive toxicity after exposure to nanoparticles. Applying computational modeling (ISD3) to better understand dose metrics for soluble nanoparticles allows for better interpretation of in vitro hazard assessments.},
doi = {10.1186/s12989-018-0283-z},
journal = {Particle and Fibre Toxicology},
issn = {1743-8977},
number = 1,
volume = 15,
place = {United States},
year = {2018},
month = {12}
}