Nanomedicine - The Economist 

November 5, 2013.

Particle physiology

http://www.economist.com/blogs/babbage/2013/11/nanomedicine?fsrc=scn/fb/wl/bl/particlephysiology

ONE of the dreams of nanotechnologists—those who try to engineer machines mere billionths of a metre across—is to build medical devices that can circulate in the bloodstream. This aspiration often prompts ridicule, frequently accompanied by a still from “Fantastic Voyage”, a film made in the 1960s about a team of doctors in a submarine that had been miniaturised with them in it, so they could destroy a blood clot which threatened to kill a scientist who had been working behind the iron curtain.

Well, titter ye not. For though Sangeeta Bhatia’s nanoscale devices are not really submarines, are certainly not crewed by Raquel Welch, and do not actually destroy blood clots, they do go around the bloodstream finding such clots, and they report back what they have found, so that destruction can take place if necessary.

Dr Bhatia is a bioengineer and physician at the Massachusetts Institute of Technology. She was impressed by the competence of modern urine testing, which can detect conditions ranging from diabetes and pregnancy to breast and brain cancer, but also noticed that one thing it cannot detect is clots attached to the walls of blood vessels. Nor is there an effective blood test for such clots.

That matters, for if a clot breaks free from its site of formation and lodges somewhere critical it can kill. A clot in the coronary artery induces a heart attack. One in a pulmonary artery causes a pulmonary embolism. One in an artery in the brain, a stroke. Dr Bhatia thought she might be able to design something that detects and reports the presence of clots and, as she outlines in ACS Nano, she has succeeded.

What Dr Bhatia’s clot-detector is actually detecting are not the clots themselves, but an enzyme called thrombin, which induces clotting and is thus an indicator of the presence of clots. Her “submarines” are tiny particles of iron oxide (though not so tiny that they pass through the kidney’s filters into the urine, and are lost). They are coated with small fragments of protein, called peptides, specially chosen because they react with thrombin. That, however, is not enough—because there is no way to tell from the outside whether such a reaction has taken place. To manage this Dr Bhatia attached reporter chemicals to the free ends of the peptides. When a peptide binds to a thrombin molecule the reporter is released. And the reporter, unlike the iron-oxide particle, is small enough to pass into the urine, where it can be detected by a simple test.

When tried out in mice, this idea worked perfectly. The urine of animals with clots in their lungs turned orange when tested, as it was supposed to do. That of clot-free animals remained unchanged. As for the iron oxide particles, these slowly dissolve in the bloodstream in a way that should cause no damage.

No trials have yet been carried out on people. But if such tests work and the procedure proves safe, then it might be used to give early warning, in those thought at risk of developing internal clots, that such clots have actually developed. They can then be attacked with clot-busting drugs before they can break away and do serious harm.