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A hundred years ago, the outbreak of the first world war saw Europe’s industrial superpowers embark on a technological arms race with increasingly lethal consequences. Over the following four years this would not only revolutionise warfare but have far-reaching consequences for communication, transport and – perhaps most surprisingly – medicine.

In 1943, American pharmacologists Louis Goodman and Alfred Gilman were investigating nitrogen mustard, a descendent of the mustard gas produced on a large scale basis by the German army in 1916, which in addition to being a blister agent had devastating effects on the immune system. Their studies found this chemical agent had the potential to prevent the replication of cancer cells, leading to the very first cancer chemotherapy regimes in the 1950s.

The limitation of chemotherapy has always been that has the potential to harm every cell in the body, rather than merely impacting the rogue tissue. However, over the past decade, the fledgling field of nanotechnology has provided researchers with a technique that may soon allow them to deliver these drugs directly to tumours.

“The reason chemotherapy doesn’t always work is because you can’t give enough of it without exposing the body to too many toxins,” explains Jack Hoopes of the Norris Cotton Cancer Centre in New Hampshire. “So you can’t get enough drug into the tumour to be effective. I think what nanotechnology offers is the ability to target things to individual cancer cells and that’s the future of cancer therapy.”

Nanoparticles are typically between 3 and 200 nanometres across, allowing them to be injected directly into the tumour for more accessible cancers, or injected in close proximity in combination with antibodies that target cancer cells.

The unique architecture of tumours’ blood supply makes it easy for them to absorb nanoparticles. There are “fenestrations” or gaps in the walls of blood vessels that opened up when the tumours formed, says Helen Townley of the Department of Engineering Science at Oxford University.

“Instead of having a nice continuous sheet of cells as you see in normal blood vessels, the arrangement is very rapid, chaotic and disorganised. These gaps are up to 300nm, so as long as our nanoparticles are smaller than that, they’re going to leave the blood vessel and enter the tumour.”

Once the nanoparticles are inside the tumour they’re likely to stay there, she says. Normal tissue is drained by lymph vessels, but tumour tissue lacks this efficient drainage system

The main aim has been to use nanoparticles to increase chemotherapy doses but researchers have been increasingly looking at additional means of destroying tumours or slowing their growth. Hoopes’s group uses iron oxide nanoparticles coated with biocompatible substances. Once inside the tumour, the iron oxide nanoparticles can be heated using an alternating magnetic field, killing it with little damage to the surrounding tissue.

“We started out primarily with breast cancer tumours in mice and we’ve been able to make this work with lots of different types of tumours,” he said. “Our most recent study has targeted mouth tumours in dogs. This cancer tends to be terminal for the dogs about five months after diagnosis so it’s highly malignant, but after inserting nanoparticles in the tumours and exposing them to the magnetic field, we’ve had quite good success.” The research has yet to be published, but Hoopes says that after just two weeks of therapy the tumours had almost disappeared.

Within the next six months he hopes to begin a phase I breast cancer trial in humans. Patients who sign up will be scheduled to have a mastectomy, enabling the researchers to examine the tissue after magnetic nanotherapy to evaluate its effectiveness.

If that proves successful then phase II will involve using a combination of magnetic nanotherapy and radiotherapy on women undergoing lumpectomy, with a future goal of being able to eradicate the tumours without any need for an operation.

Breast cancer has proved an ideal target for magnetic nanotherapy for several reasons. The tumours are accessible, easily imaged and localised, and often spread to lymph nodes, where nanoparticles tend to accumulate when injected into the bloodstream.

It is far easier to apply the magnetic field to a limb or accessible organ rather than to one that’s deep inside the body, Hoopes says. “We can be more effective and safer. For treating something like a liver tumour we have a lot of research to do on that to find ways to safely get these fields in the body.”

Researchers at Oxford University have been looking at titanium nanoparticles as a means of enhancing the effectiveness of radiotherapy. When the particles are excited by x-rays they generate high concentrations of reactive oxygen species – chemically reactive molecules that cause significant damage to cell structures leading to cell death.

“Essentially you can treat any tumour with radiotherapy if you can turn [the power] up high enough,” Townley says. “But you’ve got this therapeutic index which is the balance between damaging healthy tissue and damaging the tumour tissue. If we can get the nanoparticles into tumours where normally you wouldn’t be able to crank the radiation up high enough without severely harming the patient, we have the potential for a lower dose or a shorter course of treatment.”

Her group has also developed microparticles for another technique called chemoembolisation. The microparticles – which are about a thousand times bigger than nanoparticles – block the blood supply carrying food and oxygen to the tumour, causing the cancerous tissue to die. Nanoparticles attached to the bigger particles also deliver chemotherapy to the site of the tumour.

So far the researchers have applied their techniques in preclinical studies looking at lung cancer in mice. While lung cancer survival rates in humans have almost doubled over the past 20 years, the disease remains one of the deadliest common cancers in the UK, with five-year survival rates of less than 10% for both men and women.

“There’s a huge need for novel treatments,” Townley says. “It’s one of most untreatable cancers but in our [mice] study we found that our techniques stopped the growth of the tumour completely in its tracks while with conventional radiotherapy it still grew two and a half times in volume.”

She adds that if they can halt the growth of tough tumours like these that are resistant to radiotherapy, they can probably shrink tumours that are more sensitive it.

In the past, most cancer nanotherapy research has been aimed at enhancing the effectiveness of existing methods such as chemotherapy or radiotherapy, but in future they may be developed as standalone treatments.

“Nanotechnology is still an early science, and right now it’s most effective in human cancer patients when used in combination with other therapies, especially in these preliminary trials,” Hoopes says. “But as we improve the targeting and identify safe ways of penetrating deeper into the body, other avenues will open up.”


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