title: Silica nanoconstruct cellular toleration threshold in vitro.
abstract: The influence of geometry of silica nanomaterials on cellular uptake and toxicity on epithelial and phagocytic cells was studied. Three types of amine-terminated silica nanomaterials were prepared and characterized via the modified Stober method, namely spheres (178±27 nm), worms (232±22 nm×1348±314 nm) and cylinders (214±29 nm×428±66 nm). The findings of the study suggest that in this size range and for the cell types studied, geometry does not play a dominant role in the modes of toxicity and uptake of these particles. Rather, a concentration threshold and cell type dependent toxicity of all particle types was observed. This correlated with confocal microscopy observations, as all nanomaterials were observed to be taken up in both cell types, with a greater extent in phagocytic cells. It must be noted that there appears to be a concentration threshold at ~100 μg/mL, below which there is limited to no impact of the nanoparticles on membrane integrity, mitochondrial function, phagocytosis or cell death. Analysis of cell morphology by transmission electron microscopy, colocalization experiments with intracellular markers and Western Blot results provide evidence of potential involvement of lysosomal escape, autophagic like activity, compartmental fusion and recycling in response to intracellular nanoparticle accumulation. These processes could be involved in cellular coping or defense mechanisms. The manipulation of physicochemical properties to enhance or reduce toxicity paves the way for the safe design of silica-based nanoparticles for use in nanomedicine.
authors.affiliation: Department of Bioengineering, University of Utah, 20 South 2030 East, Salt Lake City, UT 84112, USA.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Herd
authors.forename: Alexander
authors.initials: A
authors.lastname: Malugin
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Ghandehari
mesh_terms: D000818:Animals; D001343:Autophagy; D002460:Cell Line; D002463:Cell Membrane Permeability; D049109:Cell Proliferation; D002470:Cell Survival; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D049329:Nanostructures / Q000737:chemistry* / Q000633:toxicity* / Q000648:ultrastructure; D010316:Particle Size; D012822:Silicon Dioxide / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*
chemical_list: D012822:Silicon Dioxide