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Robo-Doc

Robo-Doc

By Matthew Flavel

Researchers have unleashed swarms of nanobots that can deliver drugs directly within tumours.

Humanity has had a complicated relationship with both bacteria and robots. While many people champion “friendly” probiotic bacteria found in yogurt or domestic vacuuming robot, others have never shaken their underlying fear that bacteria, robots or both will wipe us all out.

We now need to welcome a new player to this debate: bacterial “robots” that can be controlled by magnets to fight cancer. The bacteria Magnetococcus marinus have three qualities that make this possible: they contain magnets, they are good swimmers, and they want to swim away from oxygen.

These qualities allowed researchers from Polytechnique Montréal, Université de Montréal and McGill University to steer the bacteria through the bloodstream using a magnetic field to cancerous tumours in mice. The bacteria then followed its natural behaviour, burrowing deep into the tumour where there is less oxygen. These areas are known as hypoxic zones and are resistant to most traditional therapies.

Cancer cells are up to three times more resistant to treatments such as radiotherapy in areas where oxygen is not present. Attaching the treatment to a bacteria that’s determined to find areas that lack oxygen overcomes this barrier. The small size of the bacterium allows it to make its way through the small gaps inside the tumour and into these hard-to-reach spaces, which are about 16 times thinner than a human hair.

This is the perfect place for the bacteria to dump their payload of specialised anticancer drugs. If you liken a tumour to the Death Star in Star Wars, the drug is being delivered directly into the thermal exhaust port. “These legions of nanorobotic agents were actually composed more than 100 million flagellated bacteria – and therefore self-propelled – loaded with drugs that moved by taking the most direct path between the drug’s injection point and the area of the body to cure,” said the lead researcher of the project, Prof Sylvain Martel of Polytechnique Montréal.

While bacteria were the agents of drug delivery in this case, researchers describe this field of science as nanorobotics as it involves the computer-assisted guidance of extraordinarily small “robots”. It’s important to note, however, that this specific research does not involve programming the bacteria with any sort of artificial intelligence, but rather forcing them to go where the researchers want them to go using a computer-controlled magnetic field. Once the bacteria arrive at the chosen location, they go about their usual behaviours and therefore cease being considered robotic.

Many people would expect a robot needs to be completely artificial, from its design to what it consists of and how it makes decisions. The apparent contradiction of a biological organism exhibiting its natural behaviour and a computer-controlled robot is a challenging idea, but this research blurs the lines significantly between these two seemingly distinct categories.

The way the magnetic field is applied to the bacteria is fascinating. After bacteria are injected, the mouse is placed inside a series of electric coils. When these are switched on, the resulting magnetic field can be applied to force the bacteria in whatever direction the magnetic field dictates. Change the magnetic field direction and the bacteria will follow.

So how do you get bacteria to carry something, such as a cancer treatment? It’s one thing to get the bacteria deep into a tumour, but researchers needed to overcome this question to make them useful once they arrive at their destination.

While this story is mainly about the unlikely pairing of bacteria and robotics to fight diseases such as cancer, it isn’t so much a pairing as a trio. The third unlikely factor being used to fight cancer is fat in the form of tiny packages called liposomes. What is so fantastic about liposomes is that you can put virtually any liquid inside and then send them through the body.

Researchers have been using liposomes in their work for some time, including the delivery of drugs closer to where they need to be. Until now they have been useful in delivering drugs mainly because they are able to fuse with the membranes of cells (which are also made up of lipids) and release their cargo directly into the cell. Since the drug is released directly into the cancer cells, the rest of the body isn’t exposed to these toxic chemicals along the way. Neither is the drug broken up before it reaches its target, as the lipid membrane protects it from the immune system.

These benefits of liposomes are not new findings, but the idea of loading drug-soaked liposomes with 100 million magnetic bacteria is a masterstroke. This approach to drug delivery has the potential to drastically reduce the dosage of drug needed to treat cancers. This is good news as cancer medications have a habit of being extremely toxic, so the less used the better.

The research, published in Nature Nanotechnology (http://tinyurl.com/jmhf5hc), concluded that drugs hitchhiking on the backs of magnetic bacteria were much more effective within the tumour as they were able to swim through the highly pressurised fluid found inside tumours. This is in addition to the obvious advantage of steering the drugs directly to the tumour in the first place.

The researchers also demonstrated that they can direct their microscopic army to complete other tasks, such as build a pyramid from a handful of tiny blocks. This pyramid is constructed not within mice but under a microscope in the laboratory. This level of control means we are likely to be seeing just the first of many applications for bacterial nanorobots.

The potential for this technology may be incredible, but are there any health risks associated with injecting 100 million foreign bacteria into the body? According to research co-author Dr Mahmood Mohammadi of Polytechnique Montréal: “Bacteria does not grow inside the human body and will be eliminated by the body after maximum 1 hour. It is an environmental bacteria which is not pathogenic to humans.” In other words, the bacteria will not overstay their welcome as guests in your body and will be well-behaved while they are visiting by only fighting diseases, not causing it.

That is the plan anyway, as many environmental bacteria do cause disease and their interactions with other bacteria are complex. Therefore, as usual, extensive clinical trials will still be necessary. However, this strain of bacteria did not produce an immune response in mice, which is a very strong step towards becoming a viable treatment. In addition, more research is required to understand whether this approach is just as effective in all cancers or just some.

It’s important to remember that this technology has only been trialled on mice to date, so don’t expect to be recruiting your own army of Robo-coccus for the foreseeable future.


Matthew Flavel is a PhD candidate in the Department of Physiology, Anatomy and Microbiology at La Trobe University.