One reason nanotechnology and medicine potentially make a good marriage is that the size of nano-objects is very much on the same length scale as the basic operations of cell biology; nanomedicine, therefore, has the potential to make direct interventions on living systems at the sub-cellular level. A paper in the current issue of Nature Nanotechnology (abstract, subscription required for full article) gives a very specific example, showing that the size of a drug-nanoparticle assembly directly affects how effective the drug works in controlling cell growth and death in tumour cells.
In this work, the authors bound a drug molecule to a nanoparticle, and looked at the way the size of the nanoparticle affected the interaction of the drug with receptors on the surface of target cells. The drug was herceptin, a protein molecule which binds to a receptor molecule called ErbB2 on the surface of cells from human breast cancer. Cancerous cells have too many of these receptors, and this affects the communications between different cells which tell cells whether to grow, or which marks cells for apoptosis – programmed cell death. What the authors found was that herceptin attached to gold nanoparticles was more effective than free herceptin at binding to the receptors; this then led to reduced growth rates for the treated tumour cells. But how well the effect works depends strongly on how big the nanoparticles are – best results are found for nanoparticles 40 or 50 nm in size, with 100 nm nanoparticles being barely more effective than the free drug.
What the authors think is going on is connected to the process of endocytosis, by which nanoscale particles can be engulfed by the cell membrane. Very small nanoparticles typically only have one herceptin molecule attached, so they behave much like free drug – one nanoparticle binds to one receptor. 50 nm nanoparticles have a number of herceptin molecules attached, so a single nanoparticle links together a number of receptors, and the entire complex, nanoparticles and receptors, is engulfed by the cell and taken out of the cell signalling process completely. 100 nm nanoparticles are too big to be engulfed, so only that fraction of the attached drug molecules in contact with the membrane can bind to receptors. A commentary (subscription required) by Mauro Ferrari sets this achievement in context, pointing out that a nanodrug needs to do four things: successfully navigate through the bloodstream, negotiate any biological barriers preventing it from getting it where it needs to go, locate the cell that is its target, and then to modify the pathological cellular processes that underly the disease being treated. We already know that nano-particle size is hugely important for the first three of these requirements, but this work directly connects size to the sub-cellular processes that are the target of nanomedicine.
it is too bad this is also the lenght scale where toxicity also plays a major role!…
Indeed, Eric, toxicity and therapeutic effectiveness are sometimes different sides of the same coin. Of course, in this case, it isn’t the nanoparticles by themselves that are toxic, it is the antibodies that are stuck to their surface.
that’s an interesting read. it seems nanotech is really suited for this application area. do you get unnerved with the potential abuses of nanotechnology in the medical sphere? i’d be interested in hearing your opinion.
…but don’t you think is too soon to invest in nanomedicine? Wouldn’t be better to concentrate efforts developing tools for nanotechnology in general?
Paul, you can of course imagine abuses for nanotech – if you can deliver therapeutic agents more effectively, then one can imagine less benign substances that might also be thus delivered.
MQ – I don’t think it is too soon, if one is careful about where to put one’s effort. There are already some kinds of nanomedicines on the market – see this old post for a discussion, with some examples – and others are approaching clinical approval.
Apart from brain cancers, I’ll hazard all other cancers should be treatable within a generation, by using nanomedicine to exploit difference between cancer cell and healthy cell surfaces. The blood-brain barrier and the sensitivity of the brain might make it a bit harder to treat.
R.Jones and anyone else, do you know what specific regulatory differences or other social factors (better University labs, better government or Venture Cap funding) would enable one company/scientist in one Western nation to take their treatment to market faster than in another? Are there specific FDA policies, industry practises or patent issues that give one jurisdiction an edge? Does the UK having a liberal stem-cell research policy help with regards to these cancer treatments?
nanodrug doesn’t need to do four things:
1)navigate through the bloodstream (why don’t the blood navigate to the nanodrug?),
2)”negotiate any biological barriers preventing it from getting it where it needs to go” (nature is smarter than you, if there is a barrier there’s a reason for that. work with the barrier and not against it),
3)”locate the cell that is its target” (why not locate the cause?, maybe the problem is not in the cell. is not the effect of the disease that should be treated is the cause),
4)”and then to modify the pathological cellular processes that underly the disease being treated.” (wow, if I had to design a disease my last step would look like that).
My opinion is: Just Look, Don’t Touch.
Phillip, I think one needs to be careful wishing too hard for regulatory short-cuts – let me remind you of this old cautionary tale. Human biology is complicated and very imperfectly understood, so even the most carefully targeted interventions can end up having unintended consequences. I think taking new drugs to market will, for some time to come, take a lot of time and a lot of money.
I didn’t mean to suggest cutting FDA safety concerns. More along the lines of phasing in more resources towards testing. Making sure public purses and private medical equipment/technique players are both well capitalized in the years ahead to take advantage of any science breakthroughs.
My observation is that most cancers appear to spread using a modular mechanism; is the same for all cancers. Before this thread I wasn’t aware it was cell surface receptors whose communication allowed a cancer to spread. Interfering with this communication might be be very similiar for most cancers. Transporting the magic bullet might be hard, but if all cancers spread like this, well, I’m more optimistic most cancers will be treatable by 2023 than I was previously. Cancer is a relatively dumb syndrome, not at all like AIDS in function.
Sorry that was 2033 as a prediction. And the AIDS comment was a reference that to my knowledge, cancers don’t mutate.
What I was really looking for with my post a few days ago was a shortcut to the time-consuming task of reading all the world’s FDA guidelines and historic evolutions. No such thing as a book-in-a-pill.
I’m looking forward to watching how this use of nanotechnology develops with drugs in the body. However we must be careful, I was reading an article about “Carbon nanotube health hazard” describing the health concerns of items made from nanotechnology.
The reaction from people working in manufacturing on products with carbon nanotubes like tennis racquets and paint can have problems similar to asbestos poisoning, where longer fibres are also more harmful and can cause mesothelioma – a cancer in the tissue that lines the lung. Read more over at: http://www.ed.ac.uk/news/2008/may/carbon-nanotubes
I discussed the Donaldson paper in detail in this post a few weeks ago: Asbestos-like toxicity of some carbon nanotubes.