A new bug killer


THE use and overuse of antibiotics have led to bacteria evolving resistance to many medications. Dealing with multi drug-resistant strains of Staphylococcus aureus (which causes MRSA infections) and Escherichia coli (linked to food poisoning) requires complex and costly care. The emergence of totally drug-resistant tuberculosis threatens a return to a time before antibiotics, when many life-threatening conditions were largely untreatable.

Nanotechnology could be one way of avoiding, or at least postponing, such a nightmare. Many nanoparticles, which are substances smaller than 100 nanometres (billionths of a metre) have antimicrobial properties, disrupting bacteria and either preventing them from spreading or killing them outright. Silver nanoparticles, in particular, interfere with bacterial replication and the tiniest specks physically abrade and disrupt membrane walls. The most powerful nano-attacks, however, appear to involve reactive oxygen species (ROS). These chemically active molecules are the shock troops of the biological world, rampaging through DNA, oxidising enzymes and damaging many of the cells and proteins essential for life.

The problem is that the mechanisms that allow nanoparticles to kill bacteria pose a risk to the very people they are intended to protect. Inhaled nanoparticles of metal oxides or silver can persist in the lungs and migrate to the kidneys, liver and brain with toxic effects. And ROS have been linked to genetic damage, heart problems and Alzheimer’s disease.

Now Philip Demokritou and Georgios Pyrgiotakis at the Centre for Nanotechnology and Nanotoxicology at the Harvard School of Public Health have come up with a way of creating safer nanoparticles, literally from thin air, using a process called electrospraying. A cooling element chills a tiny needle to condense a minuscule drop of water vapour from the atmosphere. Applying a high voltage to the needle then explodes the drop into a spray of droplets, each just 25 nanometres in size, containing water and ROS.

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Droplets this small would usually evaporate in a fraction of a second, and the ions within bond to organic molecules even faster. But because the condensed water is so pure, there are almost no other molecules to react with. And with the right voltage, Dr Pyrgiotakis discovered, a particle gets enough charge to boost its surface tension and resist evaporation for an hour or more. If the droplet happens to bounce into a bacterium during that time, its ROS are released to wreak havoc.

The researchers report that their nano droplets can decimate bacteria on surfaces, reducing them by a factor of between ten and nearly 100. The droplets have been tested against E.coli, S.aureus and a mycobacterium similar to the one that causes tuberculosis. In a new paper in Nanomedicine in March, they also found that an aerosol of the tiny particles, which they call nanobombs, reduced concentrations of airborne mycobacteria by over 50%. “It’s all about reducing the risk of transmission,” says Dr Demokritou. “There is not any technology out there to completely eliminate bacteria, but if you can you reduce rates by a half, that has huge implications for preventive policies.”

The researchers exposed mice to the droplets at six times the concentration used for attacking bacteria. They saw none of the biomarkers associated with lung inflammation or cellular damage from metal nanoparticles, and the mice had normal breathing. Dr Demokritou’s hypothesis is that lining fluid in the lungs of mice neutralises the nanobombs before they can penetrate to the living cells.

A personal bug shield

One of the first intended applications is replacing expensive air-disinfection systems in hospitals, which rely either on air filters that need regular maintenance or power-hungry ultraviolet lights. As the electrospray units are cheap (around $30 each) and can run on a trickle of 12-volt electricity, Dr Demokritou ultimately envisages consumer versions which plug into things like a laptop computer to create an invisible antibacterial shield for use on buses and aeroplanes.

The researchers have secured a grant from America’s Department of Agriculture to test their nanobombs on fruit and vegetables. In America leafy greens are responsible for over a fifth of all food-borne illnesses (more than any other food), despite processing that often involves nasty chemicals and unpopular irradiation treatments. Dr Demokritou believes electrospraying could be used from farm to fork to reduce pathogens like E.coli, salmonella and listeria, as well as yeasts and fungi that cause food to spoil.

Thomas Webster, director of the Nanomedicine Laboratory at Northeastern University in Boston, is impressed with the preliminary results but says the main concern is toxicity. “You have to do a good job looking at these materials and not just in the lungs,” he says. Wider environmental effects have to be considered, and whether they kill friendly bacteria.

The researchers are now planning further safety tests and will also experiment to see if electrosprayed nanoparticles can be effective against viruses like influenza. Most nanoparticles might still be too toxic to use against bacteria within the body, but if they can reduce the chance of catching an infection in the first place, that is nothing to be sneezed at.

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