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Nanoparticle agglomeration restricts uptake into living cells
Size matters when it comes to nanoparticles entering lung cells. New research published in this issue of ES&T (pp 9370–9376) shows that the finer the particles, the faster they agglomerate in biological fluids, such as the lung’s airway surface liquid. This aggregation alters the motility of the nanoparticles, with the smaller ones—which are considered the most toxic—diffusing the most slowly. The overall result is lower accumulation in cells. These results suggest that the smallest particles might be less dangerous than previously thought, because their uptake can be reduced for purely physical reasons.
“We were really surprised to find that the uptake rate at low, physiologically relevant concentrations was limited by physical transport properties in the solution rather than by the cells’ ability to engulf [cerium oxide] nanoparticles,” says Wendelin Stark, head of the functional materials laboratory at the Swiss Federal Institute of Technology Zurich and the paper’s corresponding author.
Researchers in Stark’s group exposed human lung fibroblasts—cells that form connecting tissue and are involved in the formation of asbestosis—to suspensions of different-sized cerium oxide nanoparticles, ranging in diameter from 20 to 150 nanometers (nm). They observed that the smallest particles immediately massed together. Stark says he chose to concentrate on cerium oxide powder, or ceria, because these nanoparticles are increasingly important in automotive catalystic converters as well as for industrial applications such as the polishing of computer chips.
In addition, “cells [normally] do not contain cerium; that’s why whole-cell elemental analysis makes a lot of sense,” says Silvia Diabaté, a toxicologist with the Institute of Toxicology and Genetics of the Forschungszentrum Karlsruhe (Germany). In fact, this method’s high sensitivity offers for the first time a way to explore what happens when living cells are exposed to nanoparticles at concentrations as low as 0.1 parts per million.
When they examined the cells, Stark’s group found only agglomerates of ceria nanoparticles, which were all contained in vesicles. Peter Gehr, an expert on pulmonary particle uptake and clearance at the University of Bern (Switzerland), says that in his uptake studies he has never found such vesicles enclosing the silica or polystyrene model nanoparticles that he uses. Instead, he has found particles smaller than 200 nm in diameter to be highly mobile and to cross biological membranes.
Stark says that his group’s findings are important for in vitro studies but that significant steps are still needed before the data can be applied to in vivo systems.
