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Processing Pathway Dependence of Amorphous Silica Nanoparticle Toxicity: Colloidal vs Pyrolytic
journal contribution
posted on 2016-02-20, 10:35 authored by Haiyuan Zhang, Darren
R. Dunphy, Xingmao Jiang, Huan Meng, Bingbing Sun, Derrick Tarn, Min Xue, Xiang Wang, Sijie Lin, Zhaoxia Ji, Ruibin Li, Fred
L. Garcia, Jing Yang, Martin L. Kirk, Tian Xia, Jeffrey I. Zink, Andre Nel, C. Jeffrey BrinkerWe have developed structure/toxicity relationships for
amorphous
silica nanoparticles (NPs) synthesized through low-temperature colloidal
(e.g., Stöber silica) or high-temperature pyrolysis (e.g.,
fumed silica) routes. Through combined spectroscopic and physical
analyses, we have determined the state of aggregation, hydroxyl concentration,
relative proportion of strained and unstrained siloxane rings, and
potential to generate hydroxyl radicals for Stöber and fumed
silica NPs with comparable primary particle sizes (16 nm in diameter).
On the basis of erythrocyte hemolytic assays and assessment of the
viability and ATP levels in epithelial and macrophage cells, we discovered
for fumed silica an important toxicity relationship to postsynthesis
thermal annealing or environmental exposure, whereas colloidal silicas
were essentially nontoxic under identical treatment conditions. Specifically,
we find for fumed silica a positive correlation of toxicity with hydroxyl
concentration and its potential to generate reactive oxygen species
(ROS) and cause red blood cell hemolysis. We propose fumed silica
toxicity stems from its intrinsic population of strained three-membered
rings (3MRs) along with its chainlike aggregation and hydroxyl content.
Hydrogen-bonding and electrostatic interactions of the silanol surfaces
of fumed silica aggregates with the extracellular plasma membrane
cause membrane perturbations sensed by the Nalp3 inflammasome, whose
subsequent activation leads to secretion of the cytokine IL-1β.
Hydroxyl radicals generated by the strained 3MRs in fumed silica,
but largely absent in colloidal silicas, may contribute to the inflammasome
activation. Formation of colloidal silica into aggregates mimicking
those of fumed silica had no effect on cell viability or hemolysis.
This study emphasizes that not all amorphous silicas are created equal
and that the unusual toxicity of fumed silica compared to that of
colloidal silica derives from its framework and surface chemistry
along with its fused chainlike morphology established by high-temperature
synthesis (>1300 °C) and rapid thermal quenching.