Three-layered chemical bombs may destroy previously untreatable cancers

Oncology

A medical matryoshka doll

Nov 2nd 2013 |From the print edition

TRIPLE-NEGATIVE breast cancer is one of the nastiest there is. It is hard to treat and almost always fatal. One reason treatments tend to fail is that its cells are armed with molecular pumps which remove anti-cancer drugs that manage to get inside them. But Paula Hammond, a chemical engineer at the Massachusetts Institute of Technology, thinks she can deal with this defence using triple-layered chemical bombs a few billionths of a metre across. The layers, somewhat reminiscent of a Russian matryoshka doll, first sabotage the pumps and then deliver a poisonous payload when the cells are thus unprotected.

Each bomb’s outer layer is made of hyaluronic acid, a sugary polymer that tends to accumulate in cancer cells. This layer acts as a homing device to take the bomb to its target.

The middle layer is made of RNA—specifically, a type known as small interfering RNA (siRNA) that are the products of tiny (and recently discovered) genes that do not encode proteins. It is now apparent that, contrary to what geneticists once believed, non-protein-coding genes, of which siRNAs are but a single example, greatly outnumber those that carry blueprints for proteins. The job of siRNAs is to interfere with protein production, in order to regulate it. But that means siRNAs might also be employed medically, to switch off the manufacture of a particular protein. Dr Hammond has picked one that does this to the protein of which the pumps are made.

The bomb’s inner layer, its payload, is made of a standard chemotherapy drug, doxorubicin. The theory is thus that the hyaluronic acid will guide the bomb to its target, the siRNA will disable its defences and the doxorubicin will blow it up. And so, at least in experimental mice, it proved.

As they describe in ACS Nano, Dr Hammond and her colleagues gave one of four treatments to mice that had had triple-negative breast cancer induced in them. The first treatment, an injection of saline, was a control. The others were, respectively, capsules of hyaluronic acid loaded with siRNA alone, similar capsules loaded with doxorubicin and an inactive control RNA, and the full combination of hyaluronic acid, siRNA and doxorubicin. Each treatment was given to seven mice once every five days for 15 days, and Dr Hammond monitored the tumours’ progress.

In the cases of the saline and the two partial combinations, the tumours became up to six times as big. The full combination, in contrast, caused them to shrink on average by seven-eighths—and in two mice they vanished entirely.

Mice are not women, of course, and the trial was small, so this result should be treated cautiously. But it does look promising. If bigger trials confirm it, it may open the road to a new type of therapy for cancers that were previously untreatable.

From the print edition: Science and technology