A tiny anti-cancer drug factory right inside a tumour could provide a much safer and more effective way to fight the disease, UK-based scientists have shown.
Current chemotherapy treatments flood the whole body with toxic chemicals that attack dividing cells. That not only kills cancer cells but innocent bystanders like hair follicles, cells lining the gut and the cell of the bone marrow. The side effects limit the dose of chemotherapy that can be administered.
Now Asier Unciti-Broceta says his team at the University of Edinburgh has developed a method to deliver a cancer drug that only turns deadly when it reaches the tumour. “We have developed a chemical method that allows us to eliminate the toxicity of the drug,” The technique published Nature Communications in February is surprisingly simple. Like corking a tube of poison, the cancer drug is capped with a small chemical. A small glob of palladium inserted into the tumour, acts the cork screw. Only when the cancer drug enters the tumor, is its lethal payload uncorked.
“When tumours have grown to a point where they are too big to be removed by surgery, doctors can only give massive drug doses – so high they can kill the patient,” Unciti-Broceta says. By capping the drug, much higher doses could safely be given. “To implant the palladium is very minor surgery,” he adds.
So far, the scientists have successfully trialled the idea in zebra fish, using a cancer drug called 5-fluorouracil. They completely stopped its toxic activity by capping the drug with a propargyl group. The palladium, implanted in the fish in the form of nanoparticles embedded in a ball of polystyrene resin 150 micrometres in diameter, catalysed the removal of the propargyl group to reactivate the drug.
Palladium is considered non-toxic, and is already used in dental implants.
“It’s an elegant solution,” says Anneke Blackburn, leader of the Cancer Metabolism and Genetics Group at the Australian National University in Canberra. “It will bring new life to old drugs. Designing clever ways to deliver a known drug more directly to the tumour and reduce unwanted side effects is a very economical way to improve cancer therapy.”
Before human trials can be considered, the technique will be trialled with mice, but already Unciti-Broceta has had significant interest from the pharmaceutical industry.
The technique should reach far beyond cancer treatments, he adds: “It could be applied in anything that needs local treatment of a disease, such as Parkinson’s, local infections or heart diseases.”