How safe are nanoparticles?

Nanoparticles of metal can damage the DNA inside cells even if there is no direct contact between them, scientists have found. The discovery provides an insight into how the particles might exert their influence inside the body and points to possible new ways to deliver medical treatments.

The preliminary work also raises questions about the safety of nanoparticles – which are a thousand times smaller than the width of a human hair and used in everything from sunscreens to electronics – though the researchers point out that the doses they used in their study were higher than anything a person might come into contact with.
They also said it was difficult to extrapolate results from their laboratory tests to the human body.

In the experiment, scientists from the University of Bristol grew a layer of cells and exposed one side to cobalt-chromium nanoparticles.
On the other side of this cellular barrier were human cells called fibroblasts. Though the nanoparticles never crossed the cellular barrier, they managed to damage the DNA of the fibrolasts via a cascade of biological signals in the intervening cells.
“We imagined a possibility that, in some way, that material had caused a change in the top cell layer and maybe there’s some sort of signalling going on from the top cell to the middle cell to the bottom cell,” said Patrick Case of the University of Bristol, who led the work.

Case’s team found that the DNA in the fibrolasts had around 10 times as much damage, in terms of breaks in the genetic material, compared with control conditions. DNA damage can lead to various diseases, including cancer, but Case said the changes observed in his experiments did not lead him to believe the fibrolasts were becoming cancerous.

Impact on barrier cells
The research team deliberately exposed the barrier cells in their experiment to a dose of nanoparticles thousands of times higher than anything that would occur naturally. “We used high doses of them because we wanted to make sure that the dose we used would cause damage to cells if the cells were exposed.
“When we measured the damage on the other side of the barrier, to our great surprise, not only did we see damage on the other side of the barrier but we saw as much damage as if we’d not had the barrier at all and had put the materials in contact with the cells underneath.”

The results were published in the journal Nature Nanotechnology.
Ashley Blom, head of orthopaedic surgery at the University of Bristol, said, “This work has raised some really interesting questions and given us insight into how barriers in the body might work. The body has lots of different barriers – blood-brain barrier, the skin, the lining of the gut, the placenta – and it may be that this mechanism works in some of these barriers.
“The problem is when you start translating lab work into clinical work. It never works out in the human body like it does in lab-based experiments.”
He said that the human body may contain other barriers and mechanisms that scientists still do not understand and which may counteract or enhance the mechanism found by Case.

“So I’m cautious in extrapolating this to the human body. But if barriers in the human body do work in this way, the first exciting thing is, can we deliver novel therapies across barriers without having to cross them?”
This would mean that a condition that affects the brain could be treated with something that does not cross the blood-brain barrier and does not come into contact with the brain. “There are wonderful implications for treatments using nanotechnology.”
The research also has implications for natural nanoparticles already in human bodies, which might act across membranes to trigger diseases. “Maybe small particles like prions and viruses may utilise some of these mechanisms,” said Blom.