Implementation of physiological fluids to provide insight into the characterization, fate, and biological interactions of silver nanoparticles

Abstract

Silver nanoparticles (AgNPs) are being increasingly utilized in consumer and medical applications. However, there remains conflicting reports on their safety, which are evaluated through a combination of in vitro and in vivo exposure models. These discrepancies may arise, in part, due to the inherent differences between cell-based and animal systems. It is well established that nanotoxicological effects are highly dependent on the unique physicochemical properties and behavior of the particle set, including size, surface chemistry, agglomeration, and ionic dissolution. However, recent studies have identified that these properties vary as a function of exposure environment; providing a rationale for the contradictory results between in vitro and in vivo assessments. Artificial physiological fluids are emerging as a powerful tool as they allow for the characterization of NPs in an environment which they would likely encounter in vivo, in addition to having the experimental advantages of flexibility and consistency. Here, we demonstrated that the utilization of artificial fluids provided a mechanism to assess AgNP behavior and induced bioresponses in environments that they would likely encounter in vivo. AgNPs were introduced within an alveolar-based exposure model, which included alveolar epithelial (A549) cells incubated within artificial alveolar fluid (AF). Additionally, the particles underwent extensive characterization within both AF and lysosomal fluid, which the AgNPs would encounter following cellular internalization. Following incubation in physiological environments AgNP properties were significantly modified versus a traditional media environment, including alterations to both extent of agglomeration and rate of ionic dissolution. Moreover, when A549s were exposed to AgNPs in AF, the cells displayed lower cytotoxicity and stress rates, corresponding to a fluid-dependent drop in silver ion production. This work highlights the need for enhanced in vitro models that more closely mimic in vivo exposure environments in order to capture true NP behaviors and cellular interactions.

The Effect of Silver Nanoparticles on Learning, Memory and Social Interaction in BALB/C Mice

“…AgNPs are incorporated into products or materials that are encountered daily such as water filters, fabrics, deodorants, printer ink, toothpaste, food packaging and cosmetics [3,4,5,6]. This degree of public exposure is worrisome, given that the safety of AgNPs has never been fully established and their acute and chronic toxicity remain conflicting [7,8,9]. The unregulated use of AgNPs could be a real risk, not only to public health and environment but also to the economic growth of a number of industries.…”

Characterizing the Role of Biologically Relevant Fluid Dynamics on Silver Nanoparticle Dependent Oxidative Stress in Adherent and Suspension In Vitro Models

“…As AgNPs are known to induce mammalian cytotoxicity [ 8 , 9 , 10 , 11 ], the first endpoint assessed was cellular viability, as a function of flow condition ( Figure 3 ). Starting with the A549s ( Figure 3 A), the lower AgNP dosage produced a slight cytotoxic response.…”

“…Furthermore, AgNPs have been linked to potential health concerns, with exposure resulting in significant cytotoxicity [ 7 ]. In addition to cellular death, AgNP exposure has been shown to induce numerous bioeffects including augmented oxidative stress, activation of the inflammatory and immune responses, alterations to signal transduction pathways, and genetic modifications [ 8 , 9 , 10 , 11 ]. For example, a study by Comfort et al demonstrated that, even at dosages in the pg/mL range, AgNPs were able to disrupt normal cell homeostasis by augmenting cellular stress, activating Akt and Erk signal transduction pathways, stimulating pro-inflammatory cytokine secretion, and regulating gene expression [ 9 ].…”

Simulated biological fluids – a systematic review of their biological relevance and use in relation to inhalation toxicology of particles and fibres

“…This intracellular compartment contains both chelators and precipitators known to influence solubility (Kreyling 1992), and an environment in which a number of conditions are engaged to digest the phagocytosed material. This includes a drop in pH to acidic conditions, stimulation of proteolytic lysosomal enzymes, and production of ROS to aid digestion or act as signalling molecules (generating the oxidative/respiratory burst) (Nyberg et al 1989b;Collier et al 1992;Kreyling 1992;Oberd€ orster 1993;Breitner et al 2018).…”

“…The composition of Gamble's solution, and other fluids used to simulate the neutral pH extracellular environment of the lung, is given in Table 1. Gamble's solution has been used in conjunction with other fluids, and can be found in the assessment of many materials, including man-made mineral fibres (MMMF) (Zoitos et al 1997;Guldberg et al 1998;Sebastian et al 2002), Be ore materials (bertrandite, beryl, BeSO 4 , BeO) (Deubner et al 2011), Ag NPs (Breitner et al 2018), rare earth elements (e.g. Ce, La, Nd and Gd) in refinery emissions (Gao et al 2020) and polycyclic aromatic hydrocarbons (PAHs) in coal-related particulate matter (Gao et al 2019).…”