Toxicity and safety study of silver and gold nanoparticles functionalized with cysteine and glutathione.

Barbara Pem,Ivana Vinković Vrček,Marija Ljubojević,Lea Ulm,Adela Krivohlavek,Igor M Pongrac,Ivan Pavičić,Valerije Vrček,Darija Domazet Jurašin

doi:10.3762/bjnano.10.175

Barbara Pem, Ivana Vinković Vrček + Show 7 more

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https://doi.org/10.3762/bjnano.10.175

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Abstract

This study was designed to evaluate the nano–bio interactions between endogenous biothiols (cysteine and glutathione) with biomedically relevant, metallic nanoparticles (silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs)), in order to assess the biocompatibility and fate of nanoparticles in biological systems. A systematic and comprehensive analysis revealed that the preparation of AgNPs and AuNPs in the presence of biothiols leads to nanoparticles stabilized with oxidized forms of biothiols. Their safety was tested by evaluation of cell viability, reactive oxygen species (ROS) production, apoptosis induction and DNA damage in murine fibroblast cells (L929), while ecotoxicity was tested using the aquatic model organism Daphnia magna. The toxicity of these nanoparticles was considerably lower compared to their ionic metal forms (i.e., Ag+ and Au3+). The comparison with data published on polymer-coated nanoparticles evidenced that surface modification with biothiols made them safer for the biological environment. In vitro evaluation on human cells demonstrated that the toxicity of AgNPs and AuNPs prepared in the presence of cysteine was similar to the polymer-based nanoparticles with the same core material, while the use of glutathione for nanoparticle stabilization was considerably less toxic. These results represent a significant contribution to understanding the role of biothiols on the fate and behavior of metal-based nanomaterials.

Highlights

Metallic nanoparticles (NPs) such as silver and gold have been employed in a wide range of products and applications in the biomedical field owing to their remarkable physico-chemical properties
The careful characterization of stable NPs was performed by dynamic light scattering (DLS), electrophoretic light scattering (ELS) and transmission electron microscopy (TEM) techniques
With regard to using CYS as a stabilizing agent, the results indicated that its molar concentration should be approximately ten times lower than the concentration of NaBH4, while GSH allowed for much wider concentration ranges

Summary

Introduction

Metallic nanoparticles (NPs) such as silver and gold have been employed in a wide range of products and applications in the biomedical field owing to their remarkable physico-chemical properties. In addition to the increase of papers reporting on the development of NPs for biomedical uses, the WoS search showed that there are ample in vitro and in vivo studies on the toxicity effects of AgNPs and AuNPs. There are a number of studies indicating that AgNPs negatively impact cell membranes, interfere with signaling pathways, disrupt the cell cycle, and cause mitochondrial dysfunction, oxidative stress, DNA damage and apoptosis [7,8,9]. A general consensus regarding NP toxicity is that their toxic effects cannot be conclusively defined, as the mechanism of their action depends on their physico-chemical properties (shape, size, charge, coating agents), and on the targeted cells, tissues and/or organisms as well as on the type of testing itself [34,35,36,37,38]. Exposure to NPs may lead to their uptake, translocation, and most likely, biotransformation within the body

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