DNA-seeking probes could deliver anticancer agents right to the heart of tumour cells, say chemists in Italy.

Nitric oxide (NO) is a promising anticancer agent, killing cancer cells mainly by reacting with their DNA, causing the strands to break. To deliver NO directly to DNA, Salvatore Sortino and Fiorella Callari from the University of Catania have combined a light-triggered NO donor with a DNA binding agent.

Sortino had previously developed a nitroaniline-based system, which releases NO when irradiated with visible light. To develop the new NO delivery probe, Sortino attached the nitroaniline derivative to anthracene, a flat aromatic structure known to nestle tightly into the grooves between strands in the DNA double helix. Sortino then showed that the bifunctional system did bind to DNA, and successfully released NO when triggered by light.

'The next step is to find suitable delivery vehicles to carry the NO donor into the cell compartments, and to evaluate its ability to induce DNA photorupture and phototriggered cell death,' says Sortino. 'We are also developing systems containing more intercalating and photodonor units, to improve the DNA binding affinity and light harvesting properties.'

But the potential applications of triggered NO release are not limited to cancer therapy, Sortino adds. Once thought just an environmental pollutant, NO actually controls many processes in the body, from neurotransmission to hormone secretion. 'This scenario has stimulated an explosive interest in systems able to release nitric oxide on demand,' says Sortino.

Gjumrakch Aliev, who studies the role of NO in biology at the University of Texas at San Antonio, US, agrees that controllable methods for NO release will have wide-ranging applications, including in the clinic. 'NO is a small molecule, able to cross the blood-brain barrier, so it has the potential to treat neurological disorders,' he adds.

James Mitchell Crow