Nanotechnology - Small But Deadly

[CVX]

By Christine Evans-Pughe

The Independent - UK



In his novel Prey, Michael Crichton portrayed a future threatened by minuscule, self-replicating robots that begin to consume the planet. That's still in the realm of science fiction, but not everyone believes that nanotechnology is inherently safe. The Prince of Wales, for instance, warned us a year ago that the unleashing of small-scale "nano" particles on an unprepared world could result in a Thalidomide-like health disaster.



It is not easy to dismiss such fears over the possible health effects of nanotechnology - the science of the very small, at the scale of a billionth of a metre. There may be no evidence of risk, but that does not mean that the risk is zero. In fact, only now are scientists beginning to shed some light on exactly how the specially engineered nanoparticles, which are the basic ingredients of nanotechnology, might affect our health if they managed to end up in the wider environment.



Much of this research is based on the round assembly of 60 carbon atoms known as the buckyball, or fullerene. This nanoparticle is considered important because it is a building block for all sorts of new materials and medicines. Buckyballs have remarkable characteristics. If you shoot one of these virus-sized particles at a steel plate at 15,000mph, it bounces back unharmed. Squash one, and it becomes twice as hard as diamond. They're hollow, so you can put other molecules, such as drugs, inside them.



But studies suggest that the properties that may make fullerenes useful may also make them toxic. The first evidence came earlier this year when Eva Oberdorster, an American toxicologist at the Southern Methodist University in Dallas, published a study showing how, after two days of swimming in water containing buckyballs, largemouth bass fish suffered damage to the fat membranes in their brains. Their livers had responded as though there was a toxin present.



Now, scientists at Rice University, Houston, have pinpointed what could be the mechanism causing this damage. Rice's breakthrough study, published in the journal Nano Letters, is the first to look at the toxic effects on individual human cells exposed to fullerenes, and the first to indicate the cause. "People have shown there's a hazard, but this is the first work about how that hazard comes to be. It's important for the community to understand how, because then you can change it," says Kristen Kulinowski, the director of Rice's Centre for Biological and Environmental Nanotechnology.



The Rice researchers exposed human liver and skin cells to solutions containing different concentrations of fullerenes. Four types of solution were tested. One contained plain buckyballs; in the other three, researchers modified the buckyballs by attaching other molecules to their sides.



They measured how many cells died within 48 hours, and repeated the tests until they found the exposure level for each solution that killed half the cells. The plain buckyballs destroyed half the cells in a concentration of about 20 parts per billion, but a concentration of 10 million times more was needed to make the modified fullerenes as toxic.



All atoms and molecules are surrounded by their own particular halo of electrons, but in the buckyball's case, the structure of this halo seems to be very disruptive to biological systems. "The fullerene has what is known as a high electron affinity, which means it likes to pluck electrons from other molecules it comes into contact with," says Dr Kulinowski.



When a molecule loses one electron, it's often left with a lonely partner electron. Such a molecule - a free radical - is highly reactive in its desperation to pair off. "The proposed mechanism is that these free radicals attack the cells in their search for extra electrons and damage the cell membranes," Kulinowski says. In essence, free radicals punch holes in the membranes.



The buckyballs, however, remain stable because the energy from the extra electrons they pick up seems to spread evenly over the ball-like structure. This is one of the reasons why fullerenes are so incredibly strong.



A research team at the University of Michigan has discovered a similar hole-punching effect with another, larger nanoparticle called a dendrimer, which is used in nanomedicine to deliver drugs or imaging agents to specific parts of the body via the blood. The team found that the size of the nanoparticle seemed to make a difference, with the smallest dendrimers having no adverse effects.



A member of the team, Professor Mark Banaszak Holl, says that if the presence of nanoparticles can produce holes in cell membranes, it makes it easy for all sorts of molecules, including the nanoparticle itself, to get inside the cell. "This provides a physical mechanism via which nanoparticles can be toxic to cells - even if the material the nanoparticle is made from would normally not cause chemical toxicity," he explains. This work was published in the journal Bioconjugate Chemistry last summer.



Encouragingly, both the Michigan and Rice groups have found that modifying the surface of these nanoparticles by attaching other molecules makes them far more body-friendly, and this may be a way to tune toxicity. "Attaching small molecules to the buckyball surface disrupts the electronic structure and therefore makes it less accommodating to extra electrons, so it doesn't produce as many free radicals," Kulinowski says.

Read more: http://news.independent.co.uk/world/sci ... ory=595304