Wednesday, May 06, 2015

One step closer to nano-sized cancer drug delivery


One (really tiny) step closer to nano-sized cancer drug deliveryTrigueros' recent work has focused on trying to stabilise tiny tubes made of carbon, called carbon nanotubes, which hold drugs inside the tube so they can be delivered into cancer cells. She has now found a way of keeping them stable for more than two years and in temperatures up to 42ºC. To do this, she wraps DNA around the structures, like a tortilla wraps around the fillings of a burrito. While this accomplishes the goal of keeping the nanostructures stable inside the body this doesn't do much good if the DNA can't unwrap to deliver the drugs. But, according to Trigueros, she has shown that, once inside a cell, the DNA easily unwinds and releases its payload.

When you take a drug, it travels through your bloodstream, dissolving and dispersing, and eventually reaching its designated target area. But because the blood containing the drug travels all round your body only a small percentage of the initial dose actually reaches the desired location. For over-the-counter drugs like paracetamol or ibuprofen, with very few side-effects, this doesn't matter too much. But when it comes to cancer drugs, which can affect healthy cells just as much as , this process can cause big problems. Partly because drugs are diluted in their blood, cancer patients need to take these drugs in particularly high doses – and this can cause seriously unpleasant side effects.
But Professor Sonia Trigueros, co-director of the Oxford Martin Programme on Nanotechnology, is inching closer to developing a nano-scale drug delivery system with the aim of specifically targeting cancer cells.
So how does it all work? How do the drugs get into the cancer cells? Trigueros's nanotubes exploit the differences between cancer cells and  – in this case, differences in the membranes that hold them together.
"Cancer cells are more permeable than normal cells so the nanotubes can get through the cell membrane. And once they are in, they unwrap and deliver drug," explained Trigueros.
Exploiting differences in their permeability is one way to target the cancer cells, but Trigueros explains that there is more than one way to create a truly targeted drug delivery system.
"We can attach whatever we want on DNA," she said. "So you can attach a protein that recognises cancer cells".
Trigueros has now started preliminary tests on laboratory grown , she told us during an interview. And this has shown tentative promise, she says, citing unpublished data on their effectiveness at killing these cells in the lab. Others are cautiously optimistic. "This is a really exciting prospect," says Professor Duncan Graham, nanotechnology expert and advisor to Cancer Research UK.
"A common concern with carbon nanotubes is toxicity, but when coated with DNA this concern could be removed," he explains, "and it also addresses a fundamental issue, which is that they collect into clusters that become a solid mass and so are unable to leave the body."
In theory, once Trigueros's nanotubes have finished their job they are tiny enough (50 nanometres) to be excreted through urine. This isn't the first time carbon nanotubes have been used in cancer research: a US research team has used them, for example, to target and collect images of tumours in mice. But the combination of drug delivery and cancer-specific targeting is what interests Professor Graham.
"Unlike previous work using carbon nanotubes, this approach is set to target the tumour specifically, potentially meaning fewer side effects and a lower dosage. I look forward to seeing this in animal models which is where the real proof of activity lies," he said. But he's cautious, stressing that Trigueros's work has not yet been peer-reviewed and published.


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