Tiny man-made nanoparticles have been used to successfully smuggle a powerful cancer drug into tumour cells - leaving healthy cells unharmed - in one of the first therapeutic uses for nanotechnology in living animals.
When tested in mice, the nanostructure-based therapy was 10 times as effective at delaying tumour growth, and far less toxic, than the drug given alone. The researchers believe the therapy could transform many cancers from killers into chronic, treatable diseases.
Branching polymer molecules, called dendrimers - less than five nanometres in diameter and small enough to pass through a cell membrane - were loaded with the anticancer drug methotrexate, the vitamin folic acid, and a fluorescent imaging agent.
Mice with human epithelial cell tumours on their backs, injected with the loaded nanoparticles, lived much longer than those in the control group.
"In our longest trial, which lasted 99 days, 30% - 40% of the mice given the nano-particle with methotrexate survived. All the mice receiving free methotrexate died - either from overgrowth of the tumour or from the toxic effects of the drug," says Jolanta Kukowska-Latallo, one of the researchers at the University of Michigan, US. "Effectively, we achieved a 30-day tumour delay - equivalent to about three years for a person."
The technique employs cunning Trojan horse trickery. All living cells require folic acid to replicate, but cancer cells have a particularly strong appetite for it, displaying up to one thousand more docking sites - called folate receptors - on their membranes. By attaching five folic acid molecules to branches of the dendrimer, the researchers were able to lure the cancer cells into accepting the whole package across the membrane and into the cell - including the toxic drug, which then kills off the cell.
The targeted process is far more effective than conventional chemotherapy, which relies on large concentrations of the anticancer drug in the extra-cellular fluid to slowly diffuse across the membranes, harming healthy tissue in the process.
James Baker, professor of biologic nanotechnology, who directed the study, explains: "This targeted binding gave us a million-fold improvement on drug uptake for cancer cells.
"It's the first time that we've been able to inject a therapeutic cancer treatment into the bloodstream of an animal, and have it seek out tumour cells elsewhere in the body and target them to destruction."
He says that the treatment targeted the cancer cells so successfully that they had not even found an upper dosage limit, since it had not been toxic to healthy cells.
"It will probably allow us to detoxify cancer therapy, so that instead of being a killer, cancer will become a chronic illness like diabetes - tumours will be reduced or killed off completely after large doses of this targeted treatment," Baker told New Scientist. The group is hoping to begin clinical trials in humans within 18 months, although producing the dendrimers is costly and a technically difficult process.
"These preliminary results are very interesting. They show that nanotechnology has the potential to increase the effectiveness of modern day anti-cancer drugs by specifically targeting them to cancer cells," Emma Knight, Senior Science Information Officer at Cancer Research UK, says:
But she cautions that: "However, this work is still at a very early stage. Further studies are essential to work out whether this approach could be applied to humans."
The researchers were able to determine where the dendrimers ended up in the body by following their attached fluorescent particles. They flowed freely in the extra cellular fluid - unable to cross the blood-brain barrier - before being filtered from the blood by the kidneys, and then eliminated in the mice urine.
"Brain tumours would perhaps be targeted by injecting the therapy directly into the brain," Baker says.
Journal reference: Cancer Research (vol 65, p 12)
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