The toxicity of inhaled particles of the same material often increases with aspect ratio. However, little s known with respect to the relative contributions of particle shape to mechanical damage and to clearance hindrance. We have synthesized submicron and nanoscale amorphous silica spheres and rods to examine the impact of aspect ratio on particle toxicity. In an attempt to isolate contributions from mechanical damage in vitro exposure studies were performed utilizing surface area as a dosimetric basis. Lung mechanics were simulated via a Flexercell Tension Plus system, which was used to apply a cyclic stretch of 5% elongation. The adhesion of the particles to the cell membrane was modulated by the physisorption of fibronectin (FN) to promote integrin binding and the chemisorption of polyethylene glycol (PEG) to mitigate adhesion via the prevention of protein adsorption. Quartz particles, were used as a positive control and were also surface treated. LDH and IL-8 release were used as endpoints for cytotoxicity and inflammation, respectively. Our results indicate minimal contributions from particle shape for illiciting mechanical damage in vitro; however a significant increase in LDH release and IL-8 expression were noted in stretched versus unstretched cultures in the presence of particles—cyclic stretch alone did not have a significant impact.

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