Delivering drugs with nanoparticles

03 February 2014

Interview with

Cameron Alexander, University of Nottingham

So Jeremy Baumberg of the Cambridge Nanophotonics Centre predicted that Small cell lung cancernanophotonics will become mainstream in medicine within the next decade. Perhaps one of the applications will be a system being developed by Nottingham University's Cameron Alexander, to deliver and activate nanoparticles in specific cells and tissues, he spoke to Chris Smith. 

Chris - First of all Cameron, what actually is a nanoparticle?

Cameron - Well, nanoparticles essentially are any particles that fit in a size range less than a micron. So, that's something where you can have a thousand microns in a millimetre. But it's also important to remember that nanoparticles are actually bigger than atoms. So, whilst they're very small, they're actually rather bigger than atoms. But they could be anything essentially on that size range.

Chris - What are you trying to do with them? What's the problem you're trying to solve?

Cameron - So, what we're trying to do with our nanoparticles, we've devised a system where we put together nanoparticles with long chain molecules called polymers similar to the ones that Jeremy talked about. But we attach those to strings of DNA or nucleic acids which have a sequence of bases and letters so that they encode for a particular sequence. What we do, or the idea is that we can then use that code to recognise a target molecule inside a cell. The idea behind that is that that target molecule which could be something related to a disease, a gene signal from a disease could then open up a nanoparticle and release either a cargo or which could be a therapeutic drug molecule, or a signal which might be an optical readout or some other response. So you can then use this as a combined sensor and diagnostic. But also, perhaps a therapeutic at the same time.

Chris - So, we have these tiny particles, they have a cargo in the centre and wrapped around them is some DNA. You're not using the DNA as a genetic material, but you're using the DNA because it has a specific structure and a sequence, almost like an address. It can sense if there's another piece of genetic material in the cell the particles goes in to. If the two recognise each other, this makes the particle do something.

Cameron - That's right, yes. We're using the DNA as a code. If you like, a bar code, such that one can have a very specific signal which addresses that particular code. What we do at the moment, we haven't actually put drugs in the core of these things, but we stuck the DNA with cholesterol at one end, so an oily molecule. That causes these long chains to associate together. So, there's an oily water hating core, and then the DNA strands stick out from that and on top of that, we put a covering layer which hides one of the signals and only when a specific target molecule either in the cell or in the test tube as we've shown, when that comes in and binds to the other bits of DNA, this opens up the surface of this nanoparticle, revealing a signal or a hook in our case which you can then have a readout. But of course, one could do that to release a specific drug molecule at an exact place in a cell.

Chris - So, what sorts of signals are they responding to? How is that unlocking process happening and how could you make it specific for a certain type of cell or a certain type of disease?

Cameron - Well, there's a number of ways you can do this. What you can do is you can have, if you like, a little hook on these nanoparticles which is exposed to bind to a specific cell. So, particular cells and cancer cells are very obvious examples. Sometimes what they do is they produce molecules on their surface and there are more of those molecules, sometimes there's are particular what's known as receptors which bind to particular components on these nanoparticles. Those receptors are some times more prevalent in cancer cells. They're a signal of the cancer cell. And so, of course, we could put those markers on our nanoparticles to trigger their entry into a cancer cell to deliver a drug specifically to a cancer cell rather than a normal cell.

Chris - Can they be safely injected into the bloodstream anyway, these particles?

Cameron - We've not done that with these particular particles, but there are plenty of other examples of similar based systems where they have been injected safely and they circulate for a long time. So, there's no reason to suspect that these would be in any way detrimental.

Chris - If they're not wanted in a cell, then what happens if they don't open up?

Cameron - If they don't open up, these things would be passive and harmless and they can be excreted. So of course, what one can do is, make them out of natural components which degrade over time anyway, so they're filtered out by the kidneys. So, there are ways in which you can build them from components which will degrade naturally over time. So, you have plenty of flexibility and this is the advantage of using these polymer molecules, is that you can flexibility in the design to make them respond to the signal that you want, to degrade over the time that you want.

Chris - And is it likely you could package pretty much anything inside your nanoparticle or are there certain things which you just can't put in there?

Cameron - In principle, you could package pretty well anything based on the kinds of chemistries. But of course, as we go back to the concept of nanoparticle size, I think that's something that's important to remember because whilst these things are bigger than drugs molecules, so you could put a conventional drug molecules in. You couldn't for instance put in a huge number of drug molecules. There are only a certain amount of space in the core of these systems. Of course, if you want a cancer therapeutic - you want a very potent drug in the inside. Of course, there are other things which are simply too big to fit in.

Chris - If you could address them to specific tissues, apart from just labelling up the tissue to tell, doctors or scientists, "Look. This particle's homed in on this part of the body." I presume that means you could direct a drug just to that place which spares the rest of the body being exposed to it - which would reduce side effects.

Cameron - Exactly, that's one of the key things obviously in cancer therapies, but in the other therapies as well where you want to take your drug molecules to the very specific target - either the cell itself or something inside a cell - a specific location, and therefore, not expose the rest of the body to this. So, that's a very, very key thing in cancer therapy, but in other diseases too.

Chris - And the killer "T" question, "Time", how long do you think because I think people often find it difficult to understand research timescales. You're at the stage where you're doing this in a test tube. How long do you think it'll be before you've got something you could be putting into a patient?

Cameron - I think realistically, the kind of things where you develop the materials, you're looking at the kind of five year timescale whether you've established safety. Whether you've actually got something which is fully efficacious may take a little bit longer, but obviously, I'm hedging my bets on the answer because these things can always take time. But I think the chemistries are there to make these materials. The question is, cost and of course, if something else comes along in the time which is better than what we've got at the moment.

Kat Arney - I just had a really, really quick question for Cameron. It's that I've heard that cancer cells tend to really like taking up nanoparticles. Is that true and do we know why?

Cameron - Yeah, there are some cases that nanoparticles can target cancer cells and essentially, cancer tissue is slightly more disrupted than normal tissue. So, slightly bigger things like nanoparticles can actually go into the gaps between the cells. They're not pumped out quite so quickly. So that's why they can potentially target cancer cells in general.

Kat - Because there's lots of excitement about nanoparticle therapies for cancer and it does seem quite a useful property that they do like them.

Cameron - Yes, indeed. Again of course, they can carry lots of different drug payloads so you can have combination therapies at the same time. So, there's quite a lot of potential there.

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