Pro-Inflammatory versus Immunomodulatory Effects of Silver Nanoparticles in the Lung: The Critical Role of Dose, Size and Surface Modification

Abstract

The growing use of silver nanoparticles (Ag-NPs) in consumer products raises concerns about their toxicological potential. The purpose of the study was to investigate the size- and coating-dependent pulmonary toxicity of Ag-NPs in vitro and in vivo, using an ovalbumin (OVA)-mouse allergy model. Supernatants from (5.6–45 µg/mL) Ag50-PVP, Ag200-PVP or Ag50-citrate-treated NR8383 alveolar macrophages were tested for lactate dehydrogenase and glucuronidase activity, tumor necrosis factor (TNF)-α release and reactive oxygen species (ROS) production. For the in vivo study, NPs were intratracheally instilled in non-sensitized (NS) and OVA-sensitized (S) mice (1–50 µg/mouse) prior to OVA-challenge and bronchoalveolar lavage fluid (BALF) inflammatory infiltrate was evaluated five days after challenge. In vitro results showed a dose-dependent cytotoxicity of Ag-NPs, which was highest for Ag50-polyvinilpyrrolidone (PVP), followed by Ag50-citrate, and lowest for Ag200-PVP. In vivo 10–50 µg Ag50-PVP triggered a dose-dependent pulmonary inflammatory milieu in NS and S mice, which was significantly higher in S mice and was dampened upon instillation of Ag200-PVP. Surprisingly, instillation of 1 µg Ag50-PVP significantly reduced OVA-induced inflammatory infiltrate in S mice and had no adverse effect in NS mice. Ag50-citrate showed similar beneficial effects at low concentrations and attenuated pro-inflammatory effects at high concentrations. The lung microbiome was altered by NPs instillation dependent on coating and/or mouse batch, showing the most pronounced effects upon instillation of 50 µg Ag50-citrate, which caused an increased abundance of operational taxonomic units assigned to Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria. However, no correlation with the biphasic effect of low and high Ag-NPs dose was found. Altogether, both in vitro and in vivo data on the pulmonary effects of Ag-NPs suggest the critical role of the size, dose and surface functionalization of Ag-NPs, especially in susceptible allergic individuals. From the perspective of occupational health, care should be taken by the production of Ag-NPs-containing consumer products.

Health Impact of Silver Nanoparticles: A Review of the Biodistribution and Toxicity Following Various Routes of Exposure

“…A significant dose-dependent effect of pulmonary-exposed PVP-and CT-AgNPs on cardiovascular homeostasis was also demonstrated in our recent study [166]. The mechanism through which lung injury occurs and how the physicochemical properties of inhaled AgNPs affect their interactions with the lung have recently begun to be investigated in vivo [100,158,162,163]. Along with in vitro studies, in vivo results have suggested that size, coating and dose affect pulmonary inflammation and cellular toxicity.…”

“…In this context, the use of AgNPs in cosmetics production has been estimated to reach up to 20%. In addition to cosmetics, dermal contact to wound dressings and antibacterial textiles has also shown large diffusion of AgNPs [100]. In a laboratory set up, i.v., i.p., and subcutaneous injection enables AgNPs to directly gain access into systemic circulation.…”

The Effects of Genotype × Phenotype Interactions on Silver Nanoparticle Toxicity in Organotypic Cultures of Murine Tracheal Epithelial Cells

“…68 In a similar study, Alessandrini et al exposed OVA-sensitized, female BALB/cJ mice by tracheal instillation and observed size, coating, dose, and antigen effects on AgNP-induced T2 lung inflammation in allergic mice compared to healthy mice and vehicle controls, with allergic and healthy mice also being differentially sensitive to AgNP toxicity. 69 Interestingly, the authors observed AgNP-induced T2 lung inflammation in a biphasic manner, with AgNPCIT200 and AgNPPVP200 attenuating T2 lung inflammation, and AgNPCIT50 and AgNPPVP50 exacerbating T2 lung inflammation. In the present study; we observed genotype effects to be more understated than phenotype effects on baseline characterization of organotypic cultures.…”

The Complexity of the Homeopathic Healing Response Part 2: The Role of the Homeopathic Simillimum as a Complex System in Initiating Recovery from Disease

“…92 There is also the potential for a low dose (i.e., smaller quantity or concentration) by smaller size (e.g., homeopathic potency nano-structures) interaction in producing various biological effects. 18,95 Notably, finding evidence for a given type of agent, structure, process, or signal does not preclude the concomitant existence or possible role of another one in homeopathic information capture and delivery to the organism. In physics, electrons in atoms are electromagnetic phenomena.…”