Inverting a Standard Experiment Sometimes Produces Different Results

Nanoparticles will soon be used as tiny shuttles to deliver genes to cells and drugs to tumors in a more targeted way than was possible in the past. But as the scientists prepare to use the nanoparticles in medicine, concerns have arisen about their potential toxicity.

Studies of both the applications of nanoparticles and their toxicity rely on the ability of scientists to quantify the interaction between the nanoparticles and cells, particularly the uptake (ingestion) of nanoparticles by cells.

In the standard laboratory tests of the biological activity of nanoparticles, cells are plated on the bottom of a dish and culture medium containing nanoparticles is poured on top of them.

It seems straightforward enough. But recently Washington University in St. Louis scientist Younan Xia started to worry about the in vitro experiments his lab was doing with gold nanoparticles.

What if the cells were upside down, he wondered? Would that make a difference? Would it change their uptake rate?

"People assumed that if they prepared a suspension, the suspension was going to have the same concentration everywhere, including at the surface of the cells," says Xia, PhD, the James M. McKelvey Professor in the Department of Biomedical Engineering.

A battery of experiments in Xia's lab with both the standard and upside-down setups showed that nanoparticles above certain sizes and weights will settle out. So concentrations of the nanoparticles near the cell surfaces are different from those in the bulk solution and cellular uptake rates are higher.