Nano-scale advance in targeted cancer therapy

Could nanoparticles provide promising cancer treatments?

Perhaps the biggest challenge in cancer treatment is the issue of selectivity – how to kill cancer cells while leaving healthy cells unharmed.  But many commonly used chemotherapy drugs aren’t especially selective.

As a result, patients can experience unpleasant and distressing side effects, including hair loss, sickness, tiredness and susceptibility to infections.

Modern ‘targeted’ treatments, such as Herceptin and Tarceva, are designed to lock on to particular molecules found on the surface of cancer cells, increasing their selectivity.

But the Holy Grail of cancer research – a treatment that exclusively attacks cancer cells spread throughout the body, whilst leaving the rest of our cells unharmed – is still tantalisingly out of our grasp.

But work by Cancer Research UK scientists may have just taken us a step closer to this goal, with their research into a nanotechnology-based treatment that appears to specifically target cancer cells.

Nanoparticles for cancer therapy
Andreas Schatzlein and his team at the London School of Pharmacy have been investigating curious chain-like molecules called dendrimers for several years. When dendrimers are mixed with DNA molecules or cancer drugs, they form microscopic balls called ‘nanoparticles’ – you could fit tens to hundreds of these on the head of a pin.

For reasons that no-one yet understands, these nanoparticles are highly attracted to tumours – possibly due to the unusual nature of the blood vessels that fuel cancers. They also have a tendency to build up in tumours, making them ideal candidates for smuggling substances into cancer cells.

Similar nanoparticles containing cancer drugs such as paclitaxel (Taxol) are already being tested in clinical trials, but Schatzlein and his colleagues are particularly interested in using them for gene therapy – transporting specific genes into cancer cells, causing them to make toxic proteins that can kill the cells whilst leaving the surrounding tissue unharmed.

Back in 2005, Schatzlein and his team in Glasgow used dendrimer nanoparticles to smuggle the gene carrying instructions for a toxic protein called tumour necrosis factor alpha (TNFa) into cancer cells in mice.   The results were impressive – tumours shrank, and the mice survived significantly longer than those treated with just the gene or dendrimers alone.

Where do they go?
In their latest paper the researchers have gone a step further, using a clever technique to investigate how the nanoparticles target their deadly payload to cancers that have spread around the body

To do this, the scientists injected nanoparticles carrying a so-called “reporter” gene into mice with cancer that had spread, allowing them to track where the particles ended up.  Specifically, they used a gene carrying instructions for a protein that pumps the chemical iodine into cells.

The idea is that the cancer cells take up the nanoparticles, and start producing the iodine-pumping protein. Then the scientists give tiny, harmless doses of radioactive iodine to the mice, which gets taken up by only those cancer cells where the iodine-shuttling gene has been activated. Finally, using CT scanning (which detects radioactive molecules), it’s possible to build up an impressively detailed picture of the location of the tumours throughout the bodies of the mice.

The researchers found that the activity of their reporter gene accurately highlighted tumours spread throughout the body, showing that the nanoparticles had reached their target.  They also discovered that gene activity reached a peak 24 hours after injection, then faded away – important information when it comes to designing clinical trials to test the treatment in humans.

Crucially, the scientists didn’t see a significant build-up of radioactive iodine in the liver, kidney or lungs. Again, this is important, because other chemicals used to deliver gene therapy have a strong tendency to collect in these organs, causing side effects.

Where do we go now?
This research neatly proves that – in principle at least – it is possible to deliver gene therapy to tumours throughout the body, and ‘see’ it at work.  Future treatments based on this technology would ideally use nanoparticles that combined a tumour-killing gene with the iodine reporter gene.

Of course, there’s still a lot to learn about nanoparticles, including how safe they’d be to give to people – and scientists around the world are trying to work this out.

And although the results so far are encouraging, these are still relatively early experiments using animals – we’re a few years away from clinical trials of this nano-treatment in patients.

Kat

Listen to Dr Andreas Schatzlein talking about his research.

Download mp3 file, 1.45 mins, 1.6 Mb.

References:

Chisholm, E et al (2009). Cancer-Specific Transgene Expression Mediated by Systemic Injection of Nanoparticles Cancer Research, 69 (6), 2655-2662 DOI: 10.1158/0008-5472.CAN-08-2657