The smallest nano-sized silica particles used in biomedicine and engineering likely won’t cause unexpected biological responses due to their size, according to work presented recently by the Pacific Northwest National Laboratory (PNNL). The result should allay fears that cells and tissues might react unpredictably when exposed to the finest silica nanomaterials in industrial or commercial applications.

Nanotoxicologist Brian Thrall and his colleagues found that, for the most part, size doesn’t matter. The researchers used total surface area as a measure of dose, rather than particle mass or number of particles, and observed how cultured cells responded biologically. “If you consider surface area as the dose metric, then you get similar types of responses independent of the size of the particle,” said Thrall. “That suggests the chemistry that drives the biological responses doesn’t change when you get down to the smallest nanoparticle.”

Dose Measurements

Whether or not nanoparticles are safe for human consumption is not yet clear. In some cases, previous work suggested that nanoparticles become more toxic to cells the smaller the particles get. One difficulty in measuring toxicity is that not everyone agrees on which kind of dose unit to compare. Some researchers measure the dose by total weight, some by the number of particles. Neither method distinguishes whether a nanomaterial’s toxicity is due to the inherent nature of the material or the particle size under scrutiny. “Different dose metrics give different impressions of which particles are more toxic,” said Thrall.

To find out, Thrall and his colleagues at PNNL measured the dose at which the particles caused a biological response. The biological response was either the death of the cell or a change in which genes the cell turned on and off. When the scientists calculated doses by particle number or mass, the amount needed to generate a biological response was all over the map. They discovered that the best way to pinpoint how toxic the particles are to cells was to calculate the dose based on the nanomaterial’s total surface area. Only when they considered the surface area of the dose could the researchers predict the biological response.

Smaller and Smaller

The researchers found that the biological response was very similar regardless of the size of the nanoparticles. Inside cells, some genes responded to nanoparticles by ramping up or down. More than 76% of these genes behaved the same for all nanoparticle sizes tested. This indicated to the researchers that, for these genes, the nanoparticles didn’t pick up weird chemical properties as they shrunk in size.

However, the team did find some genes for which size did matter. Smaller particles appeared to affect genes that might be involved in inflammation, while larger particles appeared to affect genes that transport positively charged atoms into cells. This latter result could be due to metals contaminating the preparation of the larger particles, Thrall suggested. Overall, the results contribute to a better understanding of what goes on at the nanoscale.

“The big fear is that you’d see unique biological pathways being affected when you get down to the nanoscale,” said Thrall. “For the most part, we didn’t see that.”

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