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Magnetic Medicine

© Can Stock Photo Inc. / teshimine

© Can Stock Photo Inc. / teshimine

By Nial Wheate

Magnetic fields could soon be used to direct drugs made with nano-sized balls of iron that take chemotherapy directly to tumours, thereby completely removing the side-effects usually associated with treatment.

When I meet new people and tell them that I work in cancer, there are always two questions that I’m immediately asked: are you going to cure cancer, and how long is it going to take? The answers are not what people expect and they’re usually thrown by my response. I tell them we already have drugs capable of curing cancer – the drugs we use now work well, but we need to use them better.

Of course, the complete answer is much more complicated as treating cancer is not like treating other diseases. Each type of cancer is different, each person’s response to treatment is different, and how early we catch the cancer is as important as the methods we have for treating it.

But when chemotherapy fails and patients relapse, it’s not because the drugs don’t work. Rather, it’s because the side-effects of the drugs are so severe we can’t give the patient enough to kill the cancer completely.

The answer may lie in targeting systems that employ magnetism to move cancer drugs right to where we want them. We’ve been doing research in this and have already achieved some very interesting results.

The majority of chemotherapy drugs act by blocking important functions inside cells, such as the production of DNA. The subsequent cascade of effects results in the cell undergoing a process called apoptosis, a form of programmed cell suicide so that the cancer actually kills itself.

The side-effects of chemotherapy arise because the drugs we use to treat cancer attack all fast-growing cells in the body. While this includes cancer cells, it also includes hair follicles, which is why people can lose their hair. It includes bone marrow, which is where the body makes new red and white blood cells, which then leads to anaemia and susceptibility to infections. Patients experience nausea, vomiting and diarrhoea because the drugs attack the rapidly growing, and replaced, linings of the stomach and the intestines. An unborn baby is a group of rapidly dividing cells, which is why treating expectant mothers can be particularly challenging.

All these side-effects act to limit the amount of drug an oncologist can prescribe. When this happens it is sometimes possible that the cancer is not fully killed and the remaining cells develop resistance to further treatment. This causes the patient to relapse weeks or months later – only one cell has to remain for a cancer to grow back.

Our team believes that if we can target the drugs we already have directly to cancers, so that they don’t attack the healthy parts of the body, then the dose of the drug that is administered can be increased and the cancers will react more predictably, and respond better, to treatment.

The Swiss Cheese Model of Cancer

There are a number of different ways that drugs can be targeted to cancer cells. One of the approaches our team is using is based on the Swiss cheese model of cancer. Healthy cells grow slowly and are well-aligned, so there are no gaps between them, so healthy cells have a smooth surface like a block of cheddar cheese. In contrast, because cancer cells grow rapidly they leave gaps within solid tumours – like the holes in Swiss cheese.

These holes are just 100 nm in width and can be used to target drugs to the cancers. When a drug is attached to a nanoparticle less than 100 nm in width, these particles become trapped in the holes and release the drug into the cancer. Because healthy cells have no gaps, these nanoparticles simply bounce off them, leaving them unharmed.

We’ve examined a number of different types of nano­particles for drug delivery. Some of these are polymers called dendrimers that resemble a ball of spaghetti. We’ve also examined carbon nanotubes, which are honeycomb-shaped cylinders that are stronger than diamond. Different types of nanoparticles have different benefits in cancer treatment, but unfortunately they also present different problems regarding their manufacture and use.

Targeting Cancers with Magnets

Of course, targeting cancers simply by taking advantage of the Swiss cheese effect isn’t perfect; it still relies on the drug randomly passing by the cancer as it travels through the bloodstream. We theorised that the drug targeting could be even better if we could actively move the drug to the site of the tumour, where it could then get trapped in the cancer’s holes. To do this we made nanoparticles from a form of iron oxide called maghemite, and coated them in a layer of gold to protect the iron core from disintegrating within the human body.

Gold is a perfect metal to use to protect the iron nano­particle core. It has been used in medicine for thousands of years and is known to be non-toxic. In fact, some gold-based medicines are still used today: auranofin is used to treat rheumatoid arthritis. By using a scanning tunnelling electron microscope, we were able visualise individual nanoparticles and see the gold coating on each iron core.

Almost 50% of the treatment regimes used in chemotherapy use drugs containing an atom of platinum. The most widely utilised platinum-based chemotherapy drug is called cisplatin, which is used in the treatment of cancers of the testis, ovaries, lungs and bladder. We attached this drug to the gold-coated nanoparticles through a commonly used polymer in medicine called polyethylene glycol. This polymer is used in many types of medicines, particularly laxatives.

In the end, the final form of our delivery system contains three different types of metal: iron, gold and platinum.

The exciting part of our research came when we tested this new delivery system using live cancer cells. We first grew human ovarian cancer cells as a layer in flat dishes. Then we placed small bar magnets underneath the dishes before adding our new drug delivery system. After letting the cells grow for a few days, we then washed the cells and stained them with dye to enable us to see where the live cells remained.

What we found was that the new nanoparticles had been drawn to the poles of the magnets, and where they had settled there were distinctive kill zones where the cancer cells had failed to grow. The cells away from the magnet’s poles remained unaffected.

With this result we envisage two potential methods of using this new delivery system. The first option is to inject or place powerful magnets into the cancer itself, thus drawing the nanoparticles to the tumour that way. Alternatively, magnets could be placed outside the body or strong magnetic fields could be aimed at the locations of the cancer.

You may wonder if using powerful magnets in this way is safe and whether the magnets have any effect on the natural functions of the body. Magnets are perfectly safe for use in medicine. Every day the human body is subjected to magnetic fields from our use of electronic equipment and through our movement through the Earth’s own magnetic field, with no adverse health effects. Of course, these magnetic fields are very weak and the strength of the magnetic fields that would be needed in cancer treatment would be much stronger.

But we also know that strong magnetic fields are also perfectly safe and are already used in modern medicine. Many hospitals use MRI scanners to diagnose injury and illness in patients. These machines use huge superconducting magnets with strengths of up to 15 Tesla, and they produce no side-effects.

The physical unit Tesla is a measure of magnetic flux density, and is named after the famous physicist Nikola Tesla. To put into perspective how strong a 15 Tesla MRI scanner is, the huge crane magnets they use at the automobile wrecker’s yards to move broken cars around have a strength of only 0.5–1 Tesla. So the use of magnets in cancer drug delivery is both safe and feasible.

The Limitless Future

The end goal of all this research is not just a new delivery system that effectively cures patients of all side-effects, it will also revolutionise the way we administer chemotherapy to patients. Currently the severe side-effects of chemotherapy drugs necessitate a stay in hospital with constant monitoring by nurses and doctors. Understandably this comes at a great financial cost to the patient, who cannot work while undergoing treatment, and to the government to run the hospitals.

If these new delivery systems can prevent the side-effects of chemotherapy then in the future the treatment of cancer may be no different to the treatment of many common diseases, like diabetes or heart disease, where treatment may be undertaken by the patient in their own home.

Of course, the design of better chemotherapy drugs that are better at killing cancers and that don’t have any side-effects themselves will always be warranted and worthy of research, but until then our team continues to focus on making the current regime of drugs available to doctors even more effective. Magnetic drug delivery might just be the way to do it.

Nial Wheate is a senior lecturer at the University of Sydney’s Faculty of Pharmacy.