Safer-by-design flame-sprayed silicon dioxide nanoparticles: the role of silanol content on ROS generation, surface activity and cytotoxicity

Abstract

BackgroundAmorphous silica nanoparticles (SiO2 NPs) have been regarded as relatively benign nanomaterials, however, this widely held opinion has been questioned in recent years by several reports on in vitro and in vivo toxicity. Surface chemistry, more specifically the surface silanol content, has been identified as an important toxicity modulator for SiO2 NPs. Here, quantitative relationships between the silanol content on SiO2 NPs, free radical generation and toxicity have been identified, with the purpose of synthesizing safer-by-design fumed silica nanoparticles.ResultsConsistent and statistically significant trends were seen between the total silanol content, cell membrane damage, and cell viability, but not with intracellular reactive oxygen species (ROS), in the macrophages RAW264.7. SiO2 NPs with lower total silanol content exhibited larger adverse cellular effects. The SAEC epithelial cell line did not show any sign of toxicity by any of the nanoparticles. Free radical generation and surface reactivity of these nanoparticles were also influenced by the temperature of combustion and total silanol content.ConclusionSurface silanol content plays an important role in cellular toxicity and surface reactivity, although it might not be the sole factor influencing fumed silica NP toxicity. It was demonstrated that synthesis conditions for SiO2 NPs influence the type and quantity of free radicals, oxidative stress, nanoparticle interaction with the biological milieu they come in contact with, and determine the specific mechanisms of toxicity. We demonstrate here that it is possible to produce much less toxic fumed silicas by modulating the synthesis conditions.

Nearly free surface silanols are the critical molecular moieties that initiate the toxicity of silica particles

“…Our NFS model does not contradict most of these hypotheses but explains some apparent inconsistencies. Most of previous investigations considered only the total content of silanols, often finding discrepancies with membranolysis or cytotoxicity (31,45). The present identification of the membranolytic activity of NFS may clarify why some dense polymorphs of crystalline silica, i.e., stishovite, were not active in toxicological studies (62).…”

“…Recently, we proposed that silanols damage the phagolysosome membranes of lung macrophages, activating the NALP3 inflammasome and, in turn, leading to the release of the proinflammatory cytokine interleukin 1β (IL-1β) (44). However, this toxic activity of silica particles did not appear simply related to the overall silanol density (31,45). Therefore, we hypothesized that, rather than silanols as a group, a specific surface silanol pattern might damage cell membranes and induce toxic responses (29).…”

“…Thus, the paradigm of silica toxicity has generally considered crystallinity as a key hazardous property for silica particles. However, the toxic activity of silica particles varies widely depending on their source and preparation methods (26,(29)(30)(31), and several exceptions contradict the critical role of crystallinity for silica toxicity (24)(25)(26)(29)(30)(31)(32)(33)(34). An example is given by pyrogenic amorphous silica that, contrary to other types of amorphous silica (e.g., Stöber silica, a colloidal silica), can induce lung inflammation (30) and increase collagen deposition after repeated dose administration in mice (35).…”

“…An example is given by pyrogenic amorphous silica that, contrary to other types of amorphous silica (e.g., Stöber silica, a colloidal silica), can induce lung inflammation (30) and increase collagen deposition after repeated dose administration in mice (35). Other studies showed that some Stöber silicas can cause inflammation in rodents (36,37), and it is possible to vary the toxicity of pyrogenic silica by adjusting the synthesis conditions (31). The identification of the origin of this variability would represent a significant advance for developing rational production and use of safer silica materials.…”

Synthesis and Physicochemical Transformations of Size‐Sorted Graphene Oxide during Simulated Digestion and Its Toxicological Assessment against an In Vitro Model of the Human Intestinal Epithelium

“…Persistent ROS generation has been mechanistically linked to chronic inflammation and tissue injury and is one of the most studied mechanisms of ENMs toxicity. [54,55] Here, at 1 µg mL −1 of administered GO concentration, there was no effect on ROS production. On the contrary, both smGO and mGO at 5 µg mL −1 of administered concentration caused a statistically significant 1.2-fold increase in ROS production over the blank FFM, respectively (p < 0.05).…”