Microscopic envelopes deliver drug to tumours

Molecular envelopes could be used to deliver an anticancer drug to tumours with fewer side effects than the drug alone, a report in the British Journal of Cancer¹ reveals.

Scientists packaged the drug, called IUdR², inside hollow balls of molecules called liposomes. The liposomes should, hopefully, prevent the drug from damaging healthy tissue as it is carried through the body.

Researchers at the Institute of Cancer Research report that packaging IUdR does not interfere with its known ability to make cancer cells in mice more sensitive to radiotherapy. If the new delivery method can be shown to work as well in patients, and to reduce the drug’s side effects, doctors could use larger doses of IUdR to boost the effectiveness of radiotherapy.

Radiotherapy is used to kill cells in tumours. But nearby healthy cells are often damaged in the process.

Scientists have developed drugs that sensitise cancer cells so that lower doses of radiation can be used to treat patients, reducing harmful side effects on normal cells.

IUdR is one such ‘radiosensitiser’, but severe side effects of its own, including bone marrow suppression, have so far prevented it from entering clinical use.

Lead researcher Dr Kevin Harrington, of the Cancer Research UK Targeted Therapy Laboratory at the Institute of Cancer Research, says: “The benefits of using liposomes to deliver a drug stem from their ability to deliver relatively more drug to where it’s wanted. The immune system doesn’t reject the liposome, and the ‘enveloped’ drug does far less harm to healthy cells than the drug on its own.

“This is the first time that liposomes have been used with this particular drug. Further work is needed, but our results suggest that in a matter of years patients could safely receive active doses of IUdR. That would enable them to receive lower levels of radiation and still kill the cancer cells in their bodies.”

Liposomes are made of the same molecules as cell membranes. This means the immune system does not identify liposomes as foreign, enabling them to pass freely through the body.

Because blood vessels in tumours are relatively leaky, more liposomes pass from the blood into tumours than into normal tissue. The liposomes in this study had extra molecules of polyethylene glycol (PEG) on the outside. These ‘pegylated’ liposomes survive in the bloodstream longer than ordinary liposomes, allowing even more of them to enter tumours.

When the liposomes release IUdR within the tumour, the cancer cells mistake it for one of the building blocks of DNA and use it when making new copies of their genes. But IUdR makes DNA unstable, and leaves the cells much more susceptible to the lethal effects of radiotherapy.

Professor John Toy, Medical Director at Cancer Research UK, which owns the British Journal of Cancer, says: “As well as developing new drugs to fight cancer, we need new and better ways to deliver therapy.”

“Reducing the side effects of this particular drug could, in turn, reduce the side effects associated with radiotherapy. Novel technologies such as liposomes offer the hope of more targeted, and therefore safer, treatments for cancer in the future.”

Read the report

1. 5-iodo-2′-deoxyuridine

ENDS

Note to Editors:

Use of ordinary IUdR in early clinical trials was first reported over ten years ago. Although it sensitised tumours to radiotherapy, its toxicity restricted the dose that could be administered to patients.

The liposome-encapsulated drug was made by SEQUUS, now owned by the pharmaceutical company, Alza.