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Bacteria coaxed to deliver chemo drugs right inside tumours
Montreal researchers use magnetic fields to direct bacteria that navigate with natural compass
Scientists at Montreal Polytechnique and McGill University report that they have developed a way to direct bacteria carrying loads of chemotherapy drugs directly into a tumour, as shown in this illustration. (Nanorobotics Laboratory/Polytechnique Montreal)

Canadian scientists say they have found a way to direct special bacteria to carry chemotherapy drugs straight into the most active part of a cancerous tumour.

That could lead to more effective cancer treatments with lower doses of drugs and fewer side-effects.

Chemotherapy drugs are designed to be highly toxic in order to kill fast-growing cancer cells. But currently, their effectiveness is limited because very little of traditional drugs actually makes it into cancerous tumours — most of it ends up in the rest of the patient's body, causing nasty side-effects, says Sylvain Martel, a professor of computer engineering at Polytechnique Montreal.

Martel, who holds a Canada Research Chair in nanorobotics, has been working for 15 years on ways to direct drugs to a tumour.

The solution he originally envisioned was using tiny robots — nanorobots — that humans could direct using magnetic fields to swim through blood vessels and deliver drugs to a particular location.

Unfortunately, he said, "This is way beyond technology.… We cannot build this kind of nanorobot."

Instinct and a helping hand

So instead, Martel turned to nature — could there be bacteria that could do the same job?

It turns out there are. Bacteria called magnetotactic cocci are equipped with a natural, built-in compass needle made of iron that helps them navigate as they swim through water using whip-like tails called flagella. That means they can be directed using a magnetic field.

MC-1 belongs to a group of bacteria called magnetotactic cocci. They're equipped with a natural, built-in compass needle made of iron that helps them navigate. (Martel et al.)

A strain called MC-1(T), originally found in a low-oxygen region of water in the Pettaquamscutt Estuary in Rhode Island, also naturally navigates toward areas of low oxygen. That's handy because the fastest-growing part of a tumour — the area that should be targeted by chemotherapy drugs — also tends to be low in oxygen, as the growing cells consume oxygen so quickly.

That means when MC-1 bacteria are near a tumour, they'll naturally navigate toward the fastest-growing cancer cells — exactly where you might want it to deliver a load of drugs.

"You target not just the tumour, but the strategic location in the tumour where you expect to have the maximum therapeutic effect," Martel said. "Their instinct is to want to go to this thing. We just help them … we give them enough freedom so they can swim around obstacles."

But how can you get bacteria to carry things for you? By using microscopic "bags" called liposomes that chemotherapy drugs could be encapsulated in.

Martel worked with collaborators at Polytechnique Montreal and McGill University to design a chemical "Velcro strap" for the bag designed to automatically stick to the coat on the outside of the bacteria.

When they mixed bacteria with the drug-containing liposomes, about 70 liposomes stuck to each bacterium.

30-minute swim through a mouse

The bacteria were then ready to test on mice with colorectal tumours.

The drug-loaded bacteria were injected a few centimetres from the tumour. The researchers used weak magnetic fields to direct the bacteria to the tumour, then relied on the bacteria's low-oxygen navigation to bring them to the most active part of the tumour.

The study was led by Sylvain Martel, a professor of computer engineering at Polytechnique Montreal, who has been trying for 15 years to develop a way to direct chemotherapy drugs to a tumour. (Polytechnique Montreal)

The bacteria only live for about 30 minutes in a mammal's body, likely because it's too hot for them, Martel said.

"They deliver the drug and they die."

Fortunately, they swim very quickly — about 200 body lengths per second. That's about 10 times faster than most other bacteria, which allows them to get to the tumour fairly quickly, Martel said.

Once the experiment was over, the researchers examined the tumour under a microscope. Special dyes allowed them to distinguish between the bacteria, the drugs and different regions of the tumour.

They found that on average, about 55 per cent of the 100 million bacteria they injected into each mouse made it to the low-oxygen areas of the tumour, they reported in the journal Nature Nanoscience this week.

While the study suggests this strategy could work, many further tests need to be done before the technology could be tested on human cancer patients.

Because it was a proof-of-concept study, the researchers haven't yet analyzed the effect of the delivered drugs on the tumour.

Nor do they know how the immune system of monkeys or humans would react to the bacterial injection.

A colorectal tumour grown in a mouse is shown in the upper left corner. The closeup on the upper right shows the fastest-growing areas, where the oxygen level is low (hypoxic). The images on the lower left show the MC-1 bacteria preferentially gathering in those areas. A closeup of an MC-1 bacterium on the lower right shows its tiny built-in compass, made of 'magnetosomes.' (Martel et al.)

They are also working to refine the delivery system to get more bacteria into the tumour and test different ways of triggering the release of the drugs once the bacteria get there.

The study was funded by the Quebec Consortium for Drug Discovery, Ecole Polytechnique, Mitacs, the Canada Research Chair program, the Natural Sciences and Engineering Research Council of Canada, the province of Quebec, the Canadian Foundation for Innovation, and the U.S. National Institutes of Health.
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