Nanotechnology is on the verge of giving doctors the ability to treat disease with cell-by-cell precision.
Cancer chemotherapy is far from subtle. It effectively means carpet-bombing the body with a toxic regimen that kills cancer cells, but also obliterates a lot of healthy cells in the process. The ultimate hope with this approach is that the cancer surrenders before the patient does.
But what if cancer drugs could be delivered directly to a tumour or an affected organ, with minimal or no interaction with any other cells in the body? And what if, at the same time, doctors could watch the interaction between drug and target in real time, enabling them to observe the impact of the treatment and immediately adjust their therapeutic approach in response?
This is the vision of nanomedicine – an emerging field that is uniting biologists, pharmacists and materials scientists in the fight to overcome what has been one of the biggest issues in cancer therapeutics: how to kill the cancer without killing the patient.
Nanomedicine explores and exploits the interactions between nanoparticles and cells.
A drug can be packaged in a carefully designed and constructed nanoparticle, and the surface of that nanoparticle then coated with something like an antibody or protein that will home in on a target found almost exclusively on the surface of a tumour cell.
Once in the body, the nanoparticle finds its way to its target and delivers its tumour-killing contents, with little or no interaction with other healthy cells.
Nanotechnologist Professor Tom Davis and polymer chemist Professor Sébastien Perrier, both joint appointments at the Monash Institute of Pharmaceutical Sciences and the University of Warwick's Department of Chemistry, are building an international research team drawn from opposite sides of the world to see just how far they can push the boundaries of nanomedicine. Their partnership is the first of the Monash–Warwick Alliance and brings together Monash University's international reputation in the field of pharmacy and nanomedicine with the University of Warwick's world-leading skills in polymer chemistry.
When less equals more
"Drug delivery is one of the main applications of nanomedicine, because you can change the biodistribution of drugs in the body and you can target the drugs to the specific sites that they need to go to," says Professor Davis, director of the Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology. "This means you can use reduced concentrations of the drug to achieve more powerful results with no side effects."
One example of this is the use of nitric oxide to treat the raised venous blood pressure in the liver that is a leading cause of death in patients with cirrhosis (advanced liver disease). Liver specialist Professor Jacob George, the Robert W. Storr Chair of Hepatic Medicine at the University of Sydney, has been working with Professor Davis to test a nanoparticle that is designed to deliver a deadly payload to a type of cell, called a stellate cell, which is responsible for this elevation in pressure.
The payload in question – nitric oxide – is extremely effective at relaxing stellate cells, thereby reducing the pressure in the venous blood flow to the liver, but it cannot be given in an untargeted fashion because of side effects.
"If you give nitric oxide to someone with liver disease, they get vasodilation in all their tissues, their blood pressure drops to their boots, and they can get dizziness and heart failure," Professor George says.
Stellate cells carry a large number of surface receptors for vitamin A, so the researchers coated the nanoparticles with vitamin A and filled them with nitric oxide.
You can use reduced concentrations of the drug to achieve more powerful results with no side effects
The idea was that the vitamin A coating would attract the nanoparticles to the stellate cells, and then nitric oxide would only be released inside those cells.
In lab tests, the nanoparticles achieved double the reduction in liver venous pressure compared with conventional drugs. The hope now is to test this approach in clinical trials on humans.
1971 - First human PET scan
1977 - First human MRI scan
The materials from which these nanoparticles are constructed play a vital role in their function and much of the research has focused on exploring the interface between nanoparticles and biology.
"It's about understanding the fundamental interaction of the nanomaterial within the body, so when we find our materials, we can really understand how the materials are going to interact with the cells, what they are going to do to the cell, how they are going to penetrate the cell," says Professor Perrier, the Monash–Warwick Chair in Polymer Chemistry at the University of Warwick.
For example, the nanoparticles could be made of an inorganic material designed to be harmlessly excreted from the body, or based on organic polymers that will degrade into benign by-products when their job is done.
"We can also make hybrids, because organic-type compounds, such as proteins or peptides, will get recognised by the body and get destroyed straight away, so by using the polymers we can hide them away from the body and deliver them through to the cells," Professor Perrier says.
Nanoparticles are also being used to explore a new frontier of medicine called "theranostics", in which doctors are able to concurrently diagnose and deliver a therapeutic agent. The ability of nanoparticles to home in on a tumour means they can be used to bring significantly greater contrast to existing imaging techniques, such as magnetic resonance imaging (MRI) or positron emission tomography (PET).
"If you think about MRI or PET, in order to see disease sites in the body, you need extra contrast, and extra contrast might come from a radionucleotide in PET, so you get a signal from the radioactivity; or with MRI, it's in a magnetic field and you enhance the magnetisation," Professor Davis explains.
Those signals can be delivered in a nanoparticle that, because of its high selectivity for cancer cells, can deliver a much clearer picture of a tumour's boundaries and activity.
Furthermore, that same nanoparticle can serve two purposes: delivering the contrast agent to the tumour and, at the same time, delivering the drug to kill the cells of that tumour. This allows doctors to see in real time the signal change from the tumour when the drug is released.
The human body
32.2 trillion cells in the body
210 varieties of cells
"You can observe that your nanoparticle gets to that site, and then you can observe the impact that the therapy has on the tissue. Then you can immediately tune your next step," Professor Davis says.
While the Monash–Warwick Alliance is still in its infancy, its first two professors are excited to see where their collaboration will lead.
"We hope to develop some chemistry that might not be quite obvious to start with, and make it approachable or achievable by anybody," Professor Perrier says. "We are laying the groundwork."