Negligible particle-specific toxicity mechanism of silver nanoparticles: The role of Ag+ ion release in the cytosol

Abstract Toxicity of silver nanoparticles (AgNPs) is supported by many observations in literature, but no mechanism details have been proved yet. Here we confirm and quantify the toxic potential of fully characterized AgNPs in HeLa and A549 cells. Notably, through a specific fluorescent probe, we de...

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Bibliographic Details
Published in:Nanomedicine 2015-04, Vol.11 (3), p.731-739
Main Authors: De Matteis, Valeria, PhD, Malvindi, Maria Ada, PhD, Galeone, Antonio, PhD, Brunetti, Virgilio, PhD, De Luca, Elisa, PhD, Kote, Sachin, MSc, Kshirsagar, Prakash, PhD, Sabella, Stefania, PhD, Bardi, Giuseppe, PhD, Pompa, Pier Paolo, PhD
Format: Article
Language:English
Subjects:
Cations, Monovalent - pharmacokinetics
Cytosol - metabolism
HeLa Cells
Humans
Internal Medicine
Ion release
Lysosomes - metabolism
Metal Nanoparticles - chemistry
Nanoparticles
Silver
Silver - chemistry
Silver - pharmacokinetics
Silver - pharmacology
Toxicity
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Summary:Abstract Toxicity of silver nanoparticles (AgNPs) is supported by many observations in literature, but no mechanism details have been proved yet. Here we confirm and quantify the toxic potential of fully characterized AgNPs in HeLa and A549 cells. Notably, through a specific fluorescent probe, we demonstrate the intracellular release of Ag+ ions in living cells after nanoparticle internalization, showing that in-situ particle degradation is promoted by the acidic lysosomal environment. The activation of metallothioneins in response to AgNPs and the possibility to reverse the main toxic pathway by Ag+ chelating agents demonstrate a cause/effect relationship between ions and cell death. We propose that endocytosed AgNPs are degraded in the lysosomes and the release of Ag+ ions in the cytosol induces cell damages, while ions released in the cell culture medium play a negligible effect. These findings will be useful to develop safer-by-design nanoparticles and proper regulatory guidelines of AgNPs. From the Clinical Editor The authors describe the toxic potential of silver nanoparticles (AgNP) in human cancer cell lines. Cell death following the application of AgNPs is dose-dependent, and it is mostly due to Ag+ ions. Further in vivo studies should be performed to gain a comprehensive picture of AgNP-toxicity in mammals.
ISSN:1549-9634
1549-9642
DOI:10.1016/j.nano.2014.11.002