Using magnetic bacteria to fight tumours

We’re going to hear about some exciting work to use bacteria as a way to kill cancers; the idea is that microbes could be armed with destructive payloads that will kill cancer cells directly and / or evoke an anti-tumour immune response at the same time. That, believe it or not, is the easier bit and century-old science. The harder problem is how to get the bugs to the right place - in appreciable numbers - in the first place. Simone Schürle has an ingenious solution: she’s using bacteria that naturally accumulate iron particles that make them magnetic. In fact, these microbes use these like compasses to guide their movements in the wild. She creates rotating magnetic fields that behave like whirlpools to trap the magnetic bugs where she wants them - in the vicinity of cancers, for instance…

Simone - So I'm a micro roboticist by training and I'm really interested in developing new techniques for more effective drug delivery, particularly for cancer therapy. So we are basically trying to engineer tiny microrobots that can deliver drugs more effectively to a tumor site. And we take inspiration by nature and actually work with bacteria and use them as a vehicle to deliver drugs to tumors.

Chris - Is there any kind of track record of this? When you say you're inspired by nature that kind of implies that we know this happens.

Simone - This idea goes a long way back. At the end of the 19th century, the American bone surgeon William Coley who discovered actually in cancer patients tumor regressions, when they also had a bacterial infection, he figured that there seems to be a natural tumor homing of bacteria where they can also have a therapeutic function such as that they would recruit immune cells. So this was the first form of immunotherapy. So what William Coley actually did when he saw that connection, he deliberately injected patients with bacteria. And for some patients that actually worked out well and he saw tumor regression and reported these cases. But for others they actually experienced a septic shock, which you can also imagine having bacteria in the bloodstream. Because of that, and also the rise of radiation therapy, this idea kind of died down. But right now we are really experiencing a renaissance of this concept because we have new tools and synthetic biology where we can take more control over bacteria and engineer them in certain ways.

Chris - When you say take more control, what do you have in mind?

Simone - Well, there's on one hand control over how they're recognized by the human body. But on the other hand, there's also control over where they go. And this is exactly where I can come in with my microrobotics control strategies. I have been working a lot with magnetic fields and magnetic control. If you have magnetically responsive bacteria, you can use magnetic fields to help them better accumulate in tumor tissue.

Chris - How do you make a bacterium magnetically sensitive?

Simone - Well, it turns out that nature already has a solution for us. There exists innately magnetic bacteria, so-called magnetotactic bacteria. These microorganisms biomineralize iron oxide nanocrystals. So these are tiny magnets that they have inside their bodies that they produce because they take up iron from their environment. And that has evolved because these bacteria actually live in the oceans. They use it to navigate with the earth magnetic fields.

Chris - Ah, so these bacteria do use magnetic fields already and they accumulate the iron in order to do that. So you are saying we use that mechanism to effectively drive the bacteria or other bacteria where we want them to go.

Simone - We can override basically the response to earth's magnetic field and take control over their direction.

Chris - I'm surprised that something which is a tiny fraction of a millimeter long <laugh> with some iron particles inside it can detect the earth's magnetic field at all and then meaningfully use it. Do we have any idea how they're doing that?

Simone - It's really the torque. They experience any magnetic material alliance in an external magnetic field. The string of iron oxide nanocrystals is like a compass needle for diamonds. We see this in also other animals that have the sense of the magnetic field at this torque that can be perceived for orientation.

Chris - How do you envisage creating fields that will guide the microbes in the right sort of way? Because it's one thing for them to be experiencing a field on the scale of a planet and just knowing up and down. For example, when you're trying to guide something in three dimensions through complex tissues inside a body environment to a site that might be, say a tumor, that's a whole different ball game.

Simone - So it's not that we are trying to give a direction like a left or right. What we do is basically we apply rotational magnetic fields at a tumor site and these bacteria behave basically like tiny rods or levels that start turning. And when they do this in circulation, in the blood circulation of these rotational magnetic fields can help them start tumbling along blood vessel walls. And this is a very important or crucial mechanism as we identified because it helps them to find gaps between blood vessels to then get out and get into tumor tissue.

Chris - I'm with you. So in essence you use a rotating magnetic field because that almost creates whirlpools. It's like little eddies which the bacteria fall into and then they roll along. And then if there is a gap that they can crawl through, they're more likely to crawl through it. So if you center that whirlpool on where the tumor is, they're gonna slow down and roll around in the tumor preferentially, which means you're gonna enhance the delivery.

Simone - I think you've put this very well, yes. <laugh>.

Chris - Does it work though? You presumably are not at the stage where you've put this into people yet, so there must be some kind of model system that you are testing this on.

Simone - Yes. So we tested this first in a Petri dish. So from the blood vessels, the cells, we were growing them just on a membrane and then we were adding our bacteria on top and starting with these rotational magnetic fields and then counting how many bacteria could make it through the cell layer. And we could see that this was significantly higher than when we would have no magnetic field. And then we went and tested this also in animal models and could see that we find a significantly higher enrichment in tumors when we exposed some to these rotational magnetic fields.