Geoff Baldwin - Building nanocages

Kat - One person who's working hard on a new biomedical application for synthetic biology is Imperial College's Geoff Baldwin. He's working on new ways to target cancer drugs specifically to tumours, leaving healthy cells unharmed, with the help of some specially-constructed nanocages.

Geoff - Normally, when you take a drug whether it's a tablet or it's injected then that drug disperses across your entire body and that's why you have toxic effects from drugs where they are acting elsewhere other than the site you want them to act. So, the general proposition is, can we make drug action more specific by targeting that drug to the site where we want it to go in the body?

Kat - So for example, if you have a cancer to make it go to that cancer and not anywhere else?

Geoff - Exactly. So, a lot of the problems associated with anticancer drugs is that they're very toxic. So, they're very good at killing cancer cells, but the problem is they're also quite good at killing other cells in your body too. That's why a lot of chemotherapy treatments for cancer have pretty nasty side effects. So, our idea is to shield these drugs by encapsulating them in a nanostructure so that these drugs, once they're administered into your body, don't have the same toxic side effects.

Kat - So, it's almost like smuggling them in to get them to just the right place.

Geoff - Indeed, yeah sort of a Trojan horse type affair where a nanocage targets them to the cell and we can direct those nanocages to specific cells. And then once they're at that site then what we want them to do is to release that toxic cargo at the site where you want the treatment.

Kat - Surprise! It's a drug!

Geoff - Yeah, indeed.

Kat - So, how are you using the tools of synthetic biology to do this? How do you make these nanocages and trap the drug inside them?

Geoff - What the approaches of synthetic biology have given us is the sort of a modular approach to biology and by treating these nanocages as modular reformable structures where we can take them apart and then rationally put them back together.

Kat - Effectively, like biological bricks.

Geoff - Yeah, because we've developed quite a lot of foundational tools in synthetic biology around assembling DNA, we can actually use that to recapitulate different modifications and different formulations of these nanocages very quickly. That has made us able to refactor and reform these nanocages and sample lots of different variations of them to pick out the ones that work best for our purposes and we can do that much more quickly and much more efficiently than we could previously.

Kat - How do you make them? Is it the kind of approach where they're being made in bacteria or yeast? How do you actually manufacture these little cages?

Geoff - We just express them in bacteria. And so, our nanocages are made of protein. So they are natural proteinaceous material. We take these nanocages from a variety of sources. Some of them are naturally human proteins but we can express them and purify them as individual proteins and then reform the nanocages from these purified proteins.

Kat - How do they know where to go when they get into the body? How do they know to go to a particular tumour or to the site of a disease?

Geoff - There are two ways that nanocages can be effective in terms of targeting. One of the ways that a number of people are exploiting in treatment of cancer cells with nanostructures is just that a lot of cancers have quite leaky vasculature.

Kat - That's the blood vessels that feed them?

Geoff - Yeah. So these small nanostructures are able to naturally leak out of the blood vessels at the site of tumours and they will have naturally an increased residence time at the sites of many cancers within the body. That's not true of all cancers, but it's certainly true of some solid tumours. The other way we're looking at is to combine these with antibodies and then use the specificity of antibodies against specific cell markers that are known to be associated with cancer cells and so that we can have more active targeting in that way. So, this is something which is currently being explored as to what are the best routes for targeting of these species.

Kat - Where in the process are these nanocages? It's always that, "How long is a piece of string" kind of question, but how far through the process from bright idea in the lab to "Here's the treatment that patients could receive"?

Geoff - We are a long way from having this as a treatment because any drug that you're going to administer into the body has a lot of regulatory hurdles. We've currently looking at developing this as an in vitro drug testing platform so to use these for delivering drugs in cells in the lab. The other area of interest we're looking at is whether we can use these within the gastrointestinal tract. So, there's a lot of difficult to treat tumours that are associated with the digestive tract - pancreatic cancers, liver cancers, oesophageal cancer - that are currently very difficult to diagnose and catch early, and treat effectively. And so, the idea of having a nanocage which is very visible, we can make these things highly fluorescent, and then you have the potential for endoscopic delivery rather than delivery through the bloodstream.

Kat - So you literally put a tube into the organ or the tumour and just like, pop! In you go.

Geoff - Yes. So, you'll be able to kind of spray the surfaces where you're trying to investigate for cancers within the patient. If they light up and stay lit up then you will know that the cancer is there and then what we are also hoping is that you can then perhaps combine that with directed therapy where once you see the tumours lit up, switch phasers to blast and then lead to drug dissolution where you want them.

Kat - Geoff Baldwin from Imperial College, London.