Gold nanoparticles can cross from the lungs into the blood, where they accumulate in fatty plaques inside arteries, according to a human study by UK and Dutch researchers.
The work provides further evidence of a link between environmental nanoparticles and cardiovascular disease, and has "major implications" for risk management of engineered nanoparticles, they say.
For the study, 14 healthy volunteers inhaled gold nanoparticles. Fifteen minutes to 24 hours after exposure, the nanoparticles showed up in blood and urine samples and could still be detected three months later. Inhaling smaller particles (5nm diameter compared with 30nm) resulted in higher numbers reaching the blood.
Separately, the team recruited 12 patients due to undergo surgery on their carotid arteries. Three inhaled gold nanoparticles before surgery and these showed up in arterial plaques.
The team approached the study from an air pollution perspective but the results apply to other exposures, especially those in the workplace, says corresponding author Mark Miller from the University of Edinburgh.
"We always suspected that nanoparticles get into the blood," said Dr Miller. "This had been shown before in animal studies but not convincingly in man. Furthermore, understanding how these particles then interact with blood vessels had not been explored."
Importantly, he says, the human results match those from rodent studies. As newer nanomaterials cannot be tested directly in humans, rodent studies are still relied on for toxicity studies.
In vitro tests in the field, he says, are also still limited. "There are lots of different in vitro techniques which can give you an idea of what nanoparticles can do but they only tell you part of the story."
The inhalation study findings have "immediate relevance" for the nanotechnology industry, suggest the researchers. For example, the biokinetics observed for gold "may also extend to other nanomaterials, including those with greater surface reactivity," they write in ACS Nano. And a better understanding of how nanomaterials cross physiological barriers, and their fate thereafter, will be "vital" for a safe-by-design approach for new nanomaterials.
The team is now delving into exactly how the nanoparticles cross into the blood. Inflammatory cells called macrophages, which gobble up pathogens, may carry the particles out of the lungs, they suggest. To test this theory, the researchers are stimulating mild lung inflammation in humans. If inflammatory cells are indeed involved in transporting the particles, they expect to see higher blood levels of gold.
In rats, they are doing the reverse experiment, knocking out the inflammatory cells and looking for a reduced passage of gold into the blood.
The work results from a collaboration between the University of Edinburgh, the Dutch National Institute for Public Health and the Environment (RIVM), VU University and Utrecht University.