NANOTECH:Understanding how nanoparticles interact with living systems is the key to using them well and safely, writes CLAIRE O'CONNELL

WORDS BY CLAIRE O'CONNELL

NANOSCIENCE HOLDS immense promise for medicine, including exquisitely sensitive diagnostics to detect the first hints of disease in the body and highly selective drugs that can target even the most stubborn of conditions.

But amid the exciting prospects for human health, a key question is whether the nano approach is safe, not just for medical applications but across the board in consumer products. So how is science addressing that question?

In order to both assess safety and to best harness the potential benefits of nanoparticles (which have one or more dimensions measuring less than 100nm), we have to first understand how they interact with living systems, and that research is underway, according to Prof Kenneth Dawson, who directs the Centre for BioNano Interactions at University College Dublin (UCD).

"There have been a lot of concerns about the need to ensure safety in the overall development of nanotechnology - you have to think more carefully," he says. "And that's what we are doing, thinking very carefully about where nanoparticles go and what they do when they get there."

Our bodies are already used to nanoparticles in the form of proteins that allow us to function as living organisms, and which are tagged in such a way that our cells can recognise and deal with them.

"Your body is built to process and understand nanoparticles, that's what we do," explains Dawson, who is professor of physical chemistry at UCD.

"And when we look at engineered nanoparticles we have moved ourselves down to that scale where proteins operate. Then if there's something on the surface of the nanoparticle that is recognisable [ by the body] it gets processed in the same way. There are good aspects and bad aspects about that."

On the plus side, we could target drugs to hard-to-reach parts of the body, like the brain. Similarly, anti-cancer drugs could be concentrated in tumours, attacking them while sparing healthy tissues and reducing side effects. We could also use diagnostic nanoparticles to detect diseases like cancer far earlier in its development in the body, says Prof Dawson.

But the very properties that opens those doors also changes the game in terms of safety, he notes. "The downside of all of this is as soon as we move into the nanoparticle domain, then we need to also think about safety issues, and we can no longer still rely on all the things we know about chemicals from the last 100 years."

In particular, Dawson and his team have made ground-breaking discoveries about how nanoparticles can draw proteins from a living system on to themselves, and this "corona" could influence what then happens to that particle. "One of the things we have learned is that nanoparticles can cover themselves with your own proteins and get caught up in the processing machinery," he explains.

More generally, research has not found much crude or acute toxicity associated with nanoparticles, says Dawson, and the focus is now shifting towards more subtle effects on living systems, like sparking inflammation, which if left unresolved over long periods could result in disease.

Two studies out last month highlight the shift: one, published in the highly visible Nature Nanotechnology, administered nanoparticles of cobalt-chromium to cells on one side of a nanoparticle-impermeable filter and found that cells on the other side of the filter showed signs of DNA damage.

The suggestion is that the cells exposed to the nanoparticles sent smaller signals across the barrier and induced effects in the untreated cells.

The UK study unleashed a flurry of headlines in the wider media and responses from scientists who called for more careful interpretation of the in-vitro research.

Another study, this time in the journal Cancer Research, described how mice that drank water containing nanoparticles of titanium dioxide (currently used in some sunscreens) showed signs of DNA damage and inflammation. The dose given to the mice equated to over 18 months of exposure to the nanoparticles in a manufacturing environment for humans. "This data suggest that we should be concerned about a potential risk of cancer or genetic disorders especially for people occupationally exposed to high concentrations of titanium dioxide nanoparticles, and that it might be prudent to limit their ingestion through non-essential drug additives, food colors, etc," write the UCLA study authors.

While such studies set headlines and experts alike buzzing, there's a danger of over-reacting to such early research seeking to better tease out the processes involved in nanoparticle interactions, notes Dawson, whose UCD centre leads BioNanoInteract consortium that links academic and industry research here on the effects of nanoparticles on living systems.

"It's a completely new domain of knowledge," he says. "I think one just needs to be systematic and progressive and understand the issues. The real answer to this of course is that the knowledge that we gain of how nanoparticles interact with living organisms is equally useful for nanomedicine and nanodiagnostics and ensuring safety.

"We are trying to understand what makes something safe, we are not there just to pour cold water on people's products. It's an ongoing process, and a very healthy one as long as the quality of the work is good."

Anti-cancer drugs could be concentrated in tumours, attacking them while sparing healthy tissues and reducing side effects