Dynamic Characteristics of Silver Nanoparticles in Physiological Fluids: Toxicological Implications

Abstract

The field of nanotoxicology has made tremendous progress identifying novel and potentially adverse biological effects following nanomaterial (NM) exposure. However, one facet yet to be satisfactorily explored is how a physiological environment modifies NM physicochemical properties, thus introducing novel complexities associated with solid phase material exposures. In this study, artificial alveolar, lysosomal, and interstitial fluids were used to identify environmental-specific modulations to the properties and behavior of hydrocarbon-coated (Ag-HC) and polysaccharide-coated (Ag-PS) silver NMs. As inhalation is a common route of exposure, an alveolar macrophage cell model with deposition dosages representing approximately 2.5 months and 10 years of occupational exposure (0.5 and 25 ng/mL, respectively) were employed. Following dispersion in the artificial fluids, the Ag-HC and Ag-PS NMs demonstrated significant alterations to morphology, aggregation patterns, and particle reactivity. However, the Ag-PS also demonstrated a loss of particle coating, which elicited increased cytotoxicity, phagocytosis, and inflammation not associated with the original Ag-PS. This study demonstrated that in a physiological system NMs undergo considerable modulation, introducing a scenario where the toxicity of NMs may increase over time due to internal bioconditions. These findings highlight the critical influence that the dynamic and insoluble nature of NMs have on bioeffects and the importance of characterizing this behavior.

Plasmonic nanoparticles and their characterization in physiological fluids

“…After 10 min of incubation the NPs are mainly localized in the aqueous lining layer formed by the cells before they are internalized. which was confirmed by transmission electron microscopy and dynamic light scattering experiments [28].…”

“…Due to their outstanding optical properties, an increasing number of studies have focused on Au for a wide range of biological and biomedical applications such as biosensing, biomedical imaging, gene and drug delivery, or disease detection [55,56]. Tables 1 and 2 summarize typical NPs, organized by the main analytical method used to characterize them in a variety of [28] Ag NPs (Bare and polysaccharide coated) Alveolar and lysosomal fluid Stability and aggregation Casals (2010) [59] Au NPs Complete cell media Evolution of protein corona Casals (2011) [60] Au and Ag NPs Complete cell media Protein corona formation and biological implications Cho (2011) [9] Au NPs (bare and PEG coated) Complete cell media Influence of sedimentation and diffusion on cellular uptake De Paoli Lacerda (2010) [61] Au NPs Protein solutions Interaction of NPs with human blood proteins Dominguez-Medina (2013) [62] Au NPs (citrate coated) PBS and BSA solutions Synthesis of advanced NPs to prevent aggregation Fatisson (2012) [63] Au NPs Complete cell media Impact of cell culture media components on stability Hühn (2013) [64] Au NPs (negatively and positively charged polymers)…”

“…Light scattering builds on the experience that an interaction between the NPs and biomolecules will be accompanied by changes in the hydrodynamic size of the particles. The constituent of the fluids may have an impact on stability [63], and therefore, the most frequent use is to answer whether the system remains stable or undergoes aggregation [13,28,59,60,65,69,75]. It has been repeatedly shown that the degree of aggregation has an impact on cellular response [70,77] and much effort is dedicated to improve the stability of NPs in such media [76].…”

Biological and environmental media control oxide nanoparticle surface composition: the roles of biological components (proteins and amino acids), inorganic oxyanions and humic acid

“…24 A general trend observed in both the cases is the high affinity of proteins toward the nanoparticle surfaces as has been discussed in several other studies. [34][35][36] Relative Affinities of Surface Adsorbed Ligands.…”

The bovine serum albumin protein corona on nanoparticles

“…For example, crystalline silicon dioxide has long been accepted as toxic, but the toxicity of amorphous silicon dioxide particles is still under debate [66]. Furthermore, which proteins are attracted to the nanoparticle to form the protein corona vary based on the properties at the nanoparticle surface, including hydrophilicity [67][68][69] and net charge [70,71]. These properties are inherent to the nanoparticle, but can also be mediated through surface functionalization [51,72], or through adsorption of solution components [73].…”