Professor Tony Ryan, Sheffield University
Kat - Now, we’ve covered all sorts of nanotechnology on our show before and an exciting new area is so-called "Soft Nanotechnology", or is it all that new? The cells in our bodies are fantastic examples of soft machines that work at the nanoscale and now scientists are attempting to copy some of that cell technology to build mini machines of their own. Now we’re joined by Professor Tony Ryan from Sheffield University. He’s one such scientist. Hello, Tony.
Tony - Hello, Kat.
Kat - Hello. So what exactly do we mean when we talk about soft nanotechnology?
Tony - It was great in the introduction when you said we learn from biology and from cell biology in particular because I’m a physical chemist and I’ve drawn my inspiration for this research and my colleague Richard Jones, basically from cell biology books. So cells, all the cells in your body are put together by a process called self-assembly and that’s where the molecules have information written into them to form structures whether they be membranes or little machines and the self-assembly is done by the molecules wiggling around, under the control of or not under the control of, by Brownian motion. So, soft nanotechnology uses self-assembly with molecules that contain information and Brownian motion to build structures just like biology does.
Kat - So would this be like proteins that kind of fold under their own steam. They’ve got the right kind of bonds in them that make them work?
Tony - If only we were that clever. Proteins have 21 building blocks and fantastic sequence and actually most of a proteins there, if a protein’s a thousand units long, most of a proteins there to hold four or five units in a specific configuration and that’s really, really hard to predict ab inicio so we make much simpler molecules with maybe, one or two or three different units, where we can program pattern formation and structures.
Kat - And are you using things based on amino acids, based on the sort of things that we see in nature?
Tony - So in our research, we’ve particularly tried to not use anything natural, okay? So what we’re trying to learn are the design principles. So we’ve used more or less extensively synthetic polymers. So we make our own molecules that show some of the features of proteins but they’re completely and utterly synthetic then we don’t have this kind of Frankenstein fear of the grey goo taking over the world and things.
Kat - And how small are we actually talking? What sort of size can you go down to?
Tony - Well, so we can exercise control at the level of molecules at the nanometre level, that so it really is nanotechnology.
Kat - And what sort of things are you using these for? What sort of applications do you think they could have?
Tony - Well, I was out with some neuroscientists earlier this week and we were discussing delivering molecules across the blood-brain barrier, which is a particularly hard thing to do. You know, the enduring image of nanotechnology is of this miniature submarine that swims around in your body, you know, a bit like the Fantastic Voyage. And it’s a very appealing movie and it’s got Raquel Welch in a scuba diving suit and things, but that really wouldn’t work. All the physics of how things happen at the level of cells, below the micron scale, mean that materials and objects behave very differently. So, a miniature submarine wouldn’t work but something that looks like a bacteria or a sperm might work to do that job of cell-by-cell delivery.
Kat - Excellent. So we could say, deliver drugs across the blood-brain barrier or maybe specifically into tumours or something like that?
Tony - Well, tumours are actually, relatively easy so…
Kat - They love nanoparticles.
Tony - Well, they do but that’s because the blood supply to tumours is generally very, very leaky. So if you put something in the blood supply then it will fall out of the blood supply where there are holes and generally there are holes around tumours so to address something to a tumour is actually done now. You can get things called stealth liposomes, okay? So they’re liposomes just like a famous cosmetics company might try and sell you, because you’re worth it. So this is a bag that’s decorated with molecules that stop the immune system attacking it and then that bag comes out of the blood supply around a tumour and just naturally collects there and that’s used to deliver doxorubicin in the clinic now.
Kat - Yeah because liposomes are another example of something that just sort of assembles itself if you get the water and the fat right, isn’t it?
Tony - Yup. So our molecules basically learn from liposomes. So we learn from lipids how to make a membrane. So what we’ve been doing is making molecules. They’re called blocko polymers. So if you think of the polymer as a piece of string, then we have a piece of string that maybe red one side and blue the other, and the red bits have water and the blue bits love it. So it makes a bi-layer so all the red bits cluster together and the blue bits protect them from the water and then they make a big sheet and the sheet wraps up to make a bag. And then as you wrap the sheets up, you can put things in the bag, okay? And these bags will float around and we’ve even designed them so that if they get taken into a cell, they go into a thing called an endosome and the endosome changes the pH and then the changing pH makes the bag explode.
Kat - Ah, very clever.
Tony - And deliver the contents and we’ve used that to transfect, actually to do gene therapy to make green fluorescent protein in a whole range of human and animal cells. And now the thing is, can we attach a little tail to one of these bags to make it swim?