Throwing fresh light on an ancient problem

A DCU researcher is developing new chemicals that, when illuminated, can destroy cancer cells, writes Gráinne Black

A DCU researcher is developing new chemicals that, when illuminated, can destroy cancer cells, writes Gráinne Black

Ancient Egyptian medicine can shed light on the subject of cancer therapy, it seems. While the Egyptians used sunlight to treat skin lesions, modern medicine is increasingly using different types of light, particularly in the treatment of cancer.

The use of light to treat cancer is known as photodynamic therapy. The principle behind it is that the cancer cells are rendered sensitive to light and then exposed to it in a controlled fashion, causing the cells to break down, says Dr Kieran Nolan of the Department of Chemical Sciences in Dublin City University. Drugs called photosensitisers are used to make the cancer cells sensitive to light, dyes that are usually administered intravenously. They circulate through the body and collect in the cancer tissue.

In this form the dye is inactive, says Dr Nolan. However, the tumour is then irradiated with light of a specific wavelength, causing the dye to become photochemically active.

READ MORE

In this activated state, the dye will react with oxygen naturally present in the cell to produce an extremely reactive form known as singlet oxygen. This singlet oxygen in turn will destroy various components of the cell, thereby destroying the cancer tissue.

A major challenge, however, is ensuring that the dye is selectively taken up by the cancer cells alone and not by other cells in the body. The drug currently used in this type of cancer therapy causes unwanted side-effects. As it circulates through the body it collects in the tumour tissue as desired, but it also builds up in the skin.

This causes the skin cells to become photosensitive so that these cells also deteriorate when exposed to light. People who undergo this type of treatment must therefore avoid sunlight, with the severity of the side-effects varying depending on the skin type of the patient.

Much research in the area has focused on overcoming these unwanted "cytotoxic" effects, says Dr Nolan. Biological tissue absorbs light within a specific range of wavelengths, so it would be desirable for the dyes used in photodynamic therapy to absorb light outside of this range.

This would also push the wavelength of the light needed for the therapy beyond that of sunlight, says Dr Nolan. This would help deal with the toxicity of the drug to skin cells as the skin simply wouldn't be exposed to the type of light required for the dye to become active.

Dr Nolan is working with a group of dyes called phthalocyanines, blue dyes commonly found in paint and pigments. The aim is to manipulate these dyes so that they absorb light "outside of the biological window", light that biological tissue is transparent to.

The phototherapeutic dyes alone may not kill off all of the cancer cells, however, and it is necessary to "enhance the kill effect of the drug", says Nolan. He is developing a way of doing this. It involves attaching an extra component, a "pro-drug" to the dye and administering the drug/dye combination. The pro-drug can be any class of drug that has anti-cancer activity. When the area is irradiated, the pro-drug is cleaved from the photosensitiser.

In the light, the dye becomes photochemically active and reacts with oxygen as before to break down the components of the cell.

In this case, however, there is a second line of attack. Once it is released from the dye the pro-drug or dark drug will also work to break down the cancer cells.

It is important to ensure that the pro-drugs are inactive until they reach the cancer tissue and further research is being done in this area.

"We are working on a unique way of shutting them off and turning them on," says Dr Nolan.

Though the principle may be the same, it is clear that phototherapy has come a long way since the time of the Egyptians.