Nanomedicine is in its infancy but stands to deliver drugs that target and kill cancer cells with few side effects. CLAIRE O'CONNELLreports
WHEN IT comes to fighting cancer, the next big weapon could be size. This month a group of scientists neatly demonstrated how minute nanoparticles with the potential to carry cancer-killing agents found their way selectively into solid tumours in mice.
It’s another boost for nanomedicine, an approach that engineers tiny particles on the scale of billionths of metres to enter cells like Trojan horses, smuggling in a payload of therapeutic drugs or genes, which are then released to fight disease.
And while nanodrugs for humans are still a long way from pharmacy shelves, the concept could ultimately develop effective and “smart” sniper-like treatments that get ushered specifically into diseased tissues and hard-to-reach parts of the body.
But first steps first. The study, published this month in the journal Cancer Research, loaded up nanoparticles of polypropylenimine with a reporter gene that lights up when it gets switched on in a cell.
When they put the nanoparticles into mice with tumours, they found the lights went on at the cancer sites, indicating that the particles had arrived and delivered.
It’s not the first time nanoparticles have successfully wormed their way into target cells, but in this case the concentrations that ended up in tumours were remarkable.
“The really quite unique thing about this work is a level of selectivity of tumour targeting that has not been observed previously. We find two orders of magnitude difference between tumour and other sites, so practically all the ‘drug’ is in the tumour,” says lead researcher Dr Andreas Schatzlein from the University of London.
“I am not aware of any technology that has shown something similar.”
Schatzlein and colleagues have also previously shown that nanoparticles armed with a cargo of cell-killing genes can reduce tumours in mice. Killing off cells so specifically could solve problems associated with more conventional medicines, he notes.
“We are trying to understand in more detail how this works because this level of specificity if translated to other medicines would essentially avoid all side effects,” he says.
But he stresses the nanoparticles are still a long way from patients: “Of course the usual caveat of man and mouse being different applies, and we have to see how well this will work in the clinic.”
Schatzlein’s hope to move nanoparticles in the direction of the clinic is shared by other researchers, including Yuri Volkov, professor of molecular medicine and an investigator at Crann in at Trinity College Dublin, who describes a recent change in focus here and collaborative efforts to research the field.
“Nanomedicine did not exist in Ireland in past years, it is only emerging now,” he says. “There had been trials of nanomaterials in biological systems, but now technology has developed and we can evaluate their risk and safety issues and start applying it to the actual benefit of the patients. So scientists around Ireland met and said it’s time to do something that’s of benefit to patients, it’s time to deliver, so there will be more focus on this drug delivery.”
Stashing the drugs in tiny nanoparticles made of fats, polymers or other materials opens up new avenues across barriers in the body, such as in the kidney, brain, liver, intestine and skin. And targeting the drugs to the area that actually needs them would mean a reduced dose and fewer side effects for the patient, explains Volkov.
“If you take simple medicines like aspirin or paracetamol, or any other drugs which you simply swallow, 99 per cent, if not more, remains unutilised until your pain starts responding.
“So everyone would like to target more specifically, whether it’s the small focus of where pain needs to be treated in the brain or a focus of cancer cells,” he says. “And nanoparticles are very powerful from this perspective.”
The approach is in its infancy now, according to Volkov, who compares the current technology in nanomedicine with the early stages of computers. “With computers at the start everyone knew it was binary code, 1-0-1-0, so it was very simple, there was no complexity, there were no 3D graphics. It’s very similar.”
But as research into using nanoparticles to fight cancer is ongoing around the world, the results are looking “promising”, says Prof Kenneth Dawson from University College Dublin, who directs the Centre for Bionanointeractions, a national platform that links academic and industry research into how nanoparticles interact with living organisms.
Using nanoparticle size itself to gain access to diseased cells is the first phase of nanomedicine, explains Dawson, but ultimately the potential lies in the next phase of creating highly-targeted nanoparticles that also come with a molecular swipe code to usher them straight in to particular cells and tissues.
“The dream of nanomedicine is to target something specifically, and that would really be to use the endogenous pathways in your body, to hitch a ride on one of these highways into cells,” he says.
“If you could do that then you would be able to send incredibly small amounts of a substance to exactly the right place and there wouldn’t be collateral damage.
“The real prize in this game is to get into the right regime, the right highway and get where you need to go, but that’s not there yet. We are still learning the rules for the highway, still learning how to get there.”