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

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.

Fate and transformation of silver nanoparticles in different biological conditions

“…This possibly implies the formation of oxidised glutathione (GSSG), as noted in our previous work [ 56 ]. The most significant changes observed were the broadening of the peaks and loss of resolution, both of which are known signs of ligand binding to the NP surface [ 57 – 59 ].…”

Silver Nanoparticles for Water Pollution Monitoring and Treatments: Ecosafety Challenge and Cellulose-Based Hybrids Solution

“…contribution of each factor [143]. Smaller particles could influence toxicity by providing a larger surface area for the particle's dissolution [144] or allow cellular internalization [145], resulting in interaction with molecular mechanisms or intracellular dissolution [146].…”

“…Additionally, additional effects can be observed as particle size decrease [141,142], even though there is no general consensus on the contribution of each factor [143]. Smaller particles could influence toxicity by providing a larger surface area for the particle's dissolution [144] or allow cellular internalization [145], resulting in interaction with molecular mechanisms or intracellular dissolution [146].…”

<p>Ecotoxicity Evaluation of Pristine and Indolicidin-coated Silver Nanoparticles in Aquatic and Terrestrial Ecosystem</p>

“…20 Moreover, some studies reported that the rate and amounts of AgNP dissolution both in biological and environmental media may depend on their physicochemical properties determined by the size, stabilization and presence of other molecules. [21][22][23][24][25][26][27][28] The AgNP toxicity has already been studied in aquatic organisms such as Daphnia magna, 26,[29][30][31][32][33] where toxicity is strongly dependent on the specific properties of the produced nanoparticles (size, capping, shape) and on their coating, which may modify their effect on living organisms; therefore, toxicity needs to be evaluated case by case on different models of aquatic organisms. 34 For instance, some researchers showed that size is crucial.…”

“…The AgNP toxicity has already been studied in aquatic organisms such as Daphnia magna , 26 , 29 – 33 where toxicity is strongly dependent on the specific properties of the produced nanoparticles (size, capping, shape) and on their coating, which may modify their effect on living organisms; therefore, toxicity needs to be evaluated case by case on different models of aquatic organisms. 34 …”