JOURNALISTS sometimes joke that the ideal headline for a science story would be something like “Black holes cure cancer”. Sadly, it will never happen. “Nanotechnology cures cancer”, though, is a pretty good runner-up, and that might just turn out to be true.

In fact, nanoparticles (ie, objects whose dimensions are measured in nanometres, or billionths of a metre) have been used to treat cancer for some time. But these treatments are mainly clever ways of packaging existing drugs, rather than truly novel therapies. For instance, Doxil, a medicine used to treat ovarian cancer, is wrapped up in naturally occurring fatty bubbles called liposomes. Taxol, a common breast-cancer drug, is similarly packaged with naturally occurring blood proteins in a product called Abraxane. In both, the packaging aids the delivery of the drug and reduces its toxic side-effects.

Now, however, a second generation of nanoparticles has entered clinical trials. Some are so good at hiding their contents away until they are needed that the treatments do not merely reduce side-effects; they actually allow what would otherwise be lethal poisons to be supplied to the tumour and the tumour only. Others do not depend on drugs at all. Instead, they act as beacons for the delivery of doses of energy that destroy cancer cells physically, rather than chemically.

One example of this second approach comes from Jennifer West's laboratory at Rice University in Houston, Texas. Building on work by her colleague Naomi Halas, Dr West has constructed gold “nanoshells” that either absorb light or scatter it, depending on their design. The shells are built on a core of silica whose shape can be adjusted to produce the desired effect. Dr West then paints a layer of gold, 15 to 20 nanometres thick, over the silica core.

Shell shock

The first nanoshells made by Dr West are designed to absorb infra-red light. When they do so, they heat up. And when they heat up, so the theory goes, they will cauterise any nearby cancer cells.

To get them to the cancer, you whip up a batch of, say, 80 trillion of them and inject it into the patient's bloodstream. The particles end up in the tumour, rather than in healthy tissue, because tumours have abnormal blood capillaries. The pores in these vessels are larger than those in healthy tissues. Make your nanoshells the right size, then, and they can pass through the capillary pores and lodge in a tumour, but not in a normal organ. Twelve to 36 hours later, when enough shells have accumulated, you insert an optical fibre into the tumour, and deliver an appropriate blast of infra-red. That heats the particles up and cooks the tumour.

This procedure, known as photothermal ablation, has undergone six years of animal testing. The results are encouraging. In mice, tumours disappeared in 10-14 days and the animals remained cancer-free thereafter. Dogs, too, gave “excellent data” according to Donald Payne, the boss of Nanospectra Biosciences, Dr West's commercial partner, although he is cagey about the details, pending publication. Nanospectra is, however, now conducting trials at three medical centres in Texas on people with head and neck cancers.

One advantage of photothermal ablation is the lack of a chemical agent. That means no toxicity. Of course, safety questions about the particles themselves remain, but Dr West and Dr Payne both say they have seen no signs of harmful symptoms. Surplus particles are cleared away by the liver, spleen and lymphatic system, or are mistaken for bacteria and eaten by macrophages, one of the types of white cell in the bloodstream. Though they may remain in those macrophages for a long time, Dr West says that this longevity does not seem to cause problems.

Nor is photothermal ablation the only way of heat-treating cancer cells. MagForce Nanotechnologies, based in Berlin, has conducted three clinical trials of anti-cancer nanoparticles made from iron oxide and is now running another five. These particles are injected directly into the target tumour, rather than relying on the leaky walls of tumour capillaries to get them to the right place. Once there, they can be heated using alternating magnetic fields that are easily tolerated by patients. According to Andreas Jordan, the firm's chief scientist, this procedure has no side-effects and shows particular promise against glioblastomas, a deadly type of brain cancer, and against prostate cancer.

Other researchers on nanoparticles, though, prefer to put their faith in drugs. CytImmune Sciences of Rockville, Maryland, has just begun a study of the efficacy of Aurimune, a solid-gold nanoparticle that carries a dose of tumour necrosis factor (TNF), a substance that has a natural tendency to stick to gold.

It is also a substance hitherto regarded as too toxic for people to tolerate. It gets its name because it attacks the blood capillaries that feed a tumour. It cannot, however, distinguish between the capillaries in a tumour and those elsewhere. With natural TNF that does not matter, since the substance is produced only in the tumour itself. But if you inject TNF directly into a patient's bloodstream he will suffer massive organ failure brought on by a precipitous fall in his blood pressure.

What's your poison?

The trick, then, is to concentrate the TNF in the tumour. That can be done surgically, by a procedure known as isolated limb perfusion. But this is complicated, and the treatment works only in about three-quarters of cases. CytImmune hopes that its method will be simpler. It intends to use Aurimune as a way of delivering TNF to the tumour site, and only to the tumour site, by employing the “leaky wall” effect to get the particles to the right place.

According to Lawrence Tamarkin, CytImmune's boss, when Aurimune was run through safety trials it was able to deliver doses of TNF that were as high or higher than those which isolated limb perfusion could manage, and without serious side-effects. The only side-effect that has been noted so far is a transient fever that can be treated with over-the-counter medicines.

Calando Pharmaceuticals, of Pasadena, California, is also packing nanoparticles with a substance previously too dangerous to use. In this case the drug is called camptothecin, and the nanoparticle is made from a strand of sugar molecules. As the camptothecin is attached to the sugar molecules, the strand folds up into a sphere, hiding the drug inside as a clenched fist might hide a pea.

The result, called Cyclosert by the firm, is being tested to see if it can prevent the progression of ovarian cancer. Some 150 patients who have completed standard chemotherapy for this disease, which would normally then be followed by a period of what is known as “watchful waiting”, will, instead, be given Cyclosert. Since ovarian cancer often recurs, that will, by dint of comparison with a control group who undergo watchful waiting alone, allow the researchers to assess whether Cyclosert reduces recurrence.

Like Nanospectra and CytImmune, Calando relies on the leaky walls of tumour capillaries to deliver its products. But nanoparticle therapies of the generation after that may be smarter. Dr West has now started attaching antibodies to her gold nanoshells. Since antibodies have specific affinities to particular proteins, any nanoshells covered in antibodies to those proteins found almost exclusively on the surfaces of tumour cells will stick to those cells and no others. That way, when the light is applied, only the unhealthy cells should be killed.

Moreover, Dr West is also working on particles that both scatter and absorb light. These would reveal the extent of any tumour if illuminated with a low-power beam. That would tell surgeons where to point a high-powered killing beam so that no cancerous tissue was missed.

It may, of course, all come to nothing. The war on cancer is being pursued on many fronts, and this is just one of them. But the idea looks promising because it is based on a general principle rather than a specific practice. This means that if one particular version fails, others might still succeed. Cynicism aside, that fact alone is worth the headline.