ScienceWise - Winter 2013

The mini Death Star

Nanotechnology in the fight against cancer

DNA is highly complex and relatively delicate molecule that can easily sustain damage from chemicals such as free radicals, ultraviolet light and other natural radiation sources in the environment. If left unchecked, such damage to DNA would rapidly limit a cell’s life-span and its ability to replicate. To get around this, cells have evolved a number of mechanisms that are able to repair damaged DNA.

However, all cells are not equal in their ability to do this. In cancer cells, many of the repair mechanisms are absent or of compromised effectiveness. This coupled with their rapid division – a process during which all cells are especially vulnerable to radiation damage – means that radiation is far more lethal to cancer cells than healthy tissue.

More than 100 years ago doctors began to notice that radiation from x-rays and radioactive materials like radium had the capability to diminish tumours. Since then radiotherapy has become a highly advanced and highly effective branch of clinical medicine.

One of the limitations of radiotherapy is that although cancer cells are more sensitive to radiation, healthy cells also suffer damage in the process. So the goal of radiotherapy is to try to localize the radiation at the tumour site. And one approach to this is to place the radioactive material inside the body itself; for example thyroid cancer treatment with internal radioactive iodine is one of the most effective of all cancer treatments, with an excellent safety profile.

In a collaboration between Sirtex Medical and the Australian National University, a new nanotechnology based radiotherapy delivery system is being developed. Professor Ross Stephens is one of the scientists working on the project. “We’re trying to fashion an internal therapy that’s highly localised and that also gives doctors flexibility in designing individual treatment plans.” He says. “Our initial focus is on liver cancer, because certain peculiarities of the blood supply to the liver, make it ideal for this kind of treatment.”

Unlike other organs in the body, the cells in a healthy liver derive the majority of their nutritional support from venous blood passing through the organ but liver tumours create their own arterial blood network. “Tumours in effect hijack the liver’s arterial supply to service their own needs,” Professor Stephens says, “But in the liver this may be their downfall.”

Blood from the heart passes through major arteries then smaller ones and finally down into in fine capillaries. At their narrowest points the individual red blood cells have to squeeze through gaps only a couple of micrometers across so that they can reach the venous blood system and circulate back to the heart. “Red blood cells have no difficulty doing this because they are quite ‘squishy’ and deformable.” Professor Stephens says, “But those narrow constrictions provide us with the perfect trap for slightly larger rigid particles.”

The current Sirtex liver cancer treatment, already in use internationally, consists of tiny resin spheres small enough to get into capillaries but too big to get out again. “The spheres can be delivered to the liver via a catheter inserted via the hepatic artery,” Professor Stephens says, “And if they’re coated with a suitable radioactive material they jam in the tumour capillaries and provide intense radiation right where it’s needed. But to make really user-friendly microspheres requires a bit of nanotechnology too.”

Modern therapeutic isotopes that have replaced radium need to be produced in nuclear reactors then transported to the hospitals where they’re needed. To be effective in radiotherapy they must also be highly active which means they have a short half-life. So there isn’t much time to mess about incorporating them into the microspheres before sending them on their way.

The novel method the researchers have developed involves trapping tiny particles of isotope in a molecular cage made of carbon atoms then using a patented process to adhere those cages to the surface of the microspheres. The process is fast, efficient and most importantly the bond is very strong so the radioactive material can’t wash off in the bloodstream and end up in the wrong part of the body.

The isotope Yttrium 90 is commonly used for internal radiation treatment because it produces energetic electrons known as beta radiation. Due to the way electrons scatter in tissue, the range of this radiation is quite short, focusing the majority of the damage very near the source. Using X-rays the catheter can be directed into the liver and the microspheres delivered into the arterial blood supply of the tumour. 

“If all liver cancers were the same that would be the end of the story,” Professor Stephens explains, “But the trouble is they’re not. Often they are multifocal or diffuse rather than just one distinct tumour and each has it’s own particular relationship to the blood supply.” 

This makes it very difficult to judge how much of the dose injected is actually reaching the tumour tissue.  To make matters worse, if too much of the dose escapes from the liver and lodges in other organs it can cause complications. So ideally, the doctor would like to be able to actually see how much of the radioactive material is going where, as it’s happening.

To achieve this, the scientists have found a way to add a second isotope to the microspheres, such as gallium 67. Gallium 67 emits gamma rays which pass right through the body and can be detected externally. By coupling gamma detectors with the X-ray it’s possible to create a superimposed three-dimensional image of both the liver and the radiation. 

“So you have two kinds of radio isotope on the microspheres. Yttrium 90 which creates intense short range beta radiation to kill the cancer and gallium 67 which emits gamma rays that a clinical scanner can detect.” Professor Stephens says, “And because you can see the location of the radiation in the gamma scan along with its intensity, you can get an excellent measure of the actual dose being applied to the tumour.”

“This is proving an excellent collaboration between university and industry,” Professor Stephens says, “And we all get the satisfaction of knowing that the science we’re doing has the potential to really help many people.”

 

 

 

 

 

 

 

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