Anti-cancer nanotechnology – a two-pronged attack

Drug delivery – and in particular the delivery of anti-cancer therapeutics – has emerged as one of the major applications of nanotechnology in medicine. There’s a nice brief review of the subject by Ruth Duncan in this month’s issue of Nano Today: – Nanomedicine gets clinical . An interesting paper in this week’s Nature reports a significant new development from Sasisekharan’s group at MIT, in which two drugs are combined in a single delivery system. This nanovector first selectively targets tumour tissue, then releases a drug which cuts off the blood supply to the tumour, isolating and starving it, and then releases a second drug which directly attacks the tumour cells.

The full article can be found here, and there’s a commentary about it here. A subscription to Nature may be required for these articles, but you can also look at the Nature’s editor’s summary and the press release from MIT.

What’s interesting about this work is the way it brings together quite a lot of different tricks to make something that is starting to look like a piece of integrated nanoengineering. You have the coupling of a drug to a polymer which slowly breaks down in water; then this drug-polymer conjugate is prepared in the form of nanoparticles. These nanoparticles are, together with a second drug, encapsulated in a liposome, a self-assembled hollow shell formed by a phospholipid sheet which has folded round on itself to form an enclosed surface. The size of these liposomes is controlled so they selectively find their way into the tumour tissue and their surfaces are decorated with hairy layers of water soluble polymers to hide them from the immune system. Individually, none of these features is novel, but their combination in an integrated nanosystem is very impressive.

Nanojury UK – finalising its conclusions

The Guardian today ran a piece about the Citizen’s Jury on Nanotechnology that I’ve been involved in, which has now had its final meeting. I’ve reported on the way the project has unfolded here (the launch), here (week 1), and here (week 3). The Guardian’s piece does a good job of conveying the diversity of points of view that are represented amongst the members of the jury. I’m looking forward to the publication of the jury’s conclusions and recommendations in September.

A better alligator clip for molecular electronics

The dream of molecular electronics is to wire up circuits using individual molecules as the basic components. A basic problem is how you connect your (typically semiconducting) molecules to the metallic connectors; the leading candidate at the moment is to use molecules with a terminal thiol (-S-H) group. Thiols stick very effectively to the surface of gold; this thiol-gold chemistry has quietly become one of the most widely used tools of today’s nanotechnologists, and has been referred to as a molecular alligator clip. But it’s not without its drawbacks; rather than bonding to a single metal ion the thiol group complexes with a group of neighbouring gold atoms, and the electrical properties of the bond through the single linking sulphur atom aren’t ideal. Two papers in this week’s Science magazine suggest an alternative.

The two papers – by Siaj and McBreen (Université Laval, Québec) and Nuckolls and coworkers (Columbia University) (subscription required for access to the full articles) both describe ways of getting a molecule linked to a metal surface by a double bond (i.e. M=C- where M is a metal atom and C is the terminal carbon of an organic molecule). The surface bonded organic molecule can then be used to initiate polymerisation by a method known as ring opening metathesis polymerisation (ROMP). This is vey interesting because ROMP provides a way of growing organic semiconducting molecules with great precision. In short, we have here a better alligator clip for wiring up molecular electronics.

Soft Machines at the Foresight Conference

The newly relaunched Foresight Institute – now officially the Foresight Nanotech Institute, with a mission of “Advancing Beneficial Nanotechnology” – holds its annual conference from October 22 to 27th in San Francisco. I was very pleased to get an invitation to talk in the first part of the meeting – the Vision Weekend. I’ll be taking the opportunity to set out some of my more speculative thoughts about how we might learn lessons from nature to make a radical nanotechnology based on some of the design principles used by cell biology.

Bacterial nanowires

Electrical phenomena are important in biology, as Galvani discovered long ago when he learnt to make dead frogs twitch. But in biology electrical currents are generally carried by currents of ions rather than electrons. The transport of electrons is important in processes like photosynthesis, but the distances over which the electrons are transported are very small – the nanometer or two that defines the thickness of a lipid membrane. So the discovery of what look like electrically conducting nanowires in a soil bacterium is rather surprising. The discovery, from a group at UMASS Amherst (press release here), was reported in Nature (subscription required for full article) a few weeks ago.

The bacteria in question are soil bacteria that make their living by metabolising iron; to do this they seem to have evolved electrically conducting filaments called pili that allow them to do electrochemistry at a distance on a particle of iron oxide. Pili are common in many types of bacteria; they’re used by pathogenic bacteria to inject toxins into host cells, and for transfer of DNA between bacteria. They’re composed of protein molecules which self-assemble into long filaments, which are anchored into the bacterial cell wall by a large protein complex.

This report still leaves some unanswered questions in my mind. The conductivity of the pili was measured using atomic force microscope based conductance mapping of a graphite surface decorated with pili that had been broken off bacterial surfaces; it would be more convincing (though much more difficult) to quantify the conductivity along the length of the filament, rather than across the thickness. More importantly, perhaps, it doesn’t yet seem to be clear what is the structural feature of the pilus-making protein in this particular bacteria that leads to its electrical conductivity (as opposed to pili from other types of bacteria, which are shown in the paper to be non-conductive). It’s still a remarkable and suggestive result, though.

Thanks to Jim Moore for a comment drawing my attention to this press release.

Nano cosmetics make the headlines

This week’s Sunday Times ran a story headlined “Safety fears over ‘nano’ anti-ageing cosmetics”. The story highlights the company L’Oreal, which, it says, is “marketing a range of skin treatments containing tiny nano- particles, despite concerns about their possible long-term effects on the human body “, and singles out the product Revitalift, which apparently contains “nanosomes” of pro-retinol A. The article quotes both the FDA and the Royal Society on potential unknown health effects, quoting the latter as saying “We don’t know whether these particles are taken down through the skin and what the long-term effects might be in the bloodstream.” There’s an important point that needs clarifying here.

We need to distinguish between manufactured nanoparticles, like the zinc oxide particles mentioned as being used in some sunscreens, and self-assembled nanostructures, like nanosomes, which are the major subject of the article. It’s the manufactured nanoparticles that have given rise to the health anxieties; nanosomes are quite different. Nanosomes are formed from soap like molecules which self-assemble into water into sheets. If you can persuade these sheets to curve round and make a closed surface you have a liposome; a bag in which you can trap useful molecules like the various vitamins and vitamin precursors that companies like L’Oreal like to put in their products (see here for L’Oreal’s own description of this technology). A nanosome is simply a small liposome. The idea is that these molecular delivery bags will both protect the active molecules and help them penetrate the skin. Should we worry that these nanoparticles will enter the human body and lead to long-term adverse effects? Probably not, because the molecules that make up the bag are identical to or very similar to naturally occuring lipids (in fact, the starting point for most liposomes is lecithin, a naturally occurring mixture of phospholipids that’s very commonly used as food emulsifier), and the structures they form are held together by rather weak forces. Liposomes have been much studied as possible drug delivery agents, and this research shows that most liposomes have a rather short life-time in the body. In fact, from the point of view of drug delivery, the lifetimes are rather too short and special tricks are needed – such as the so-called stealth lipsome technology – to prevent the body recognizing and destroying them.

I’m not sure where this piece has come from – it’s written, not by a science correspondent or an environment correspondent, but by the “Social Affairs” editor. I think “Social Affairs” is a rather pretentious categorisation for all those lifestyle pieces that Sunday newspapers are plagued by, and sure enough the “Style” supplement has a consumer review of non-surgical anti-ageing treatments. Perhaps someone in the lifestyle department saw the nano- word, dimly remembered that nanotechnology had been “derided by the Prince of Wales as ‘grey goo’ “, and saw the chance to get a serious story in the paper for a change.

Will the association of these cosmetics with scare stories about the dangers of nanotechnology be bad for their sales? Somehow I doubt it. Given the popularity of botox, it seems that a combination of outrageous expense and the suggestion of danger is exactly what sells an anti-ageing treatment.

An open debate about radical nanotechnology

A public debate about nanotechnology – Nanotechnology: Radical New Science or Plus ca Change? – has been organised by Philip Moriarty at the University of Nottingham as part of a Surface Science Summer School at 4.30 pm on Wednesday 24th August . The themes of the debate are:

  • Are nanofactories capable of manufacturing virtually anything with little or no environmental impact really just a few decades away, as some groups are claiming?
  • Is nanotechnology based on scaled-down everyday engineering concepts viable or should we look to biology for insights into how to tame the nanoworld?
  • Are there potential risks associated with the manipulation of matter at the atomic and molecular levels and how might those risks be controlled?
  • Or, is nanotechnology simply a buzzword for science which, far from being a radical departure from what has gone before, simply represents a natural convergence of the conventional disciplines…?
  • The panel includes myself and J. Storrs Hall, author of the recently published book Nanofuture: What’s next for nanotechnology. As it happens, Nanofuture was part of my holiday reading, so I know that we will be getting a robust and wholehearted defense of the Drexlerian position. In addition, we have a science policy expert from the thinktank Demos who has been studying public perceptions of nanotechnology, Jack Stilgoe, and further names to be announced.

    The primary audience for the debate will be young graduate students doing PhDs in nanoscience, so we can be sure that there’ll be a vigorous technical discussion. But anyone’s welcome to turn up (Philip asks that you drop him an email – see his personal web-page for an address – if you want to come). And if you can’t make it in person, submit your question online via this link.

    (Updated 13 July following Philip’s information below that Dave King can’t now come to the Summer School)

    Nanotechnology in the developing world – an emerging south-south gap?

    Critics of nanotechnology like the ETC group worry about the potential for this new technology to lead to a divergence in wealth between rich countries and poor countries – the North-South gap. A different perspective emerges from an interesting recent commentary in the July 1 edition of Science Magazine by Mohamed Hassan of The Academy of Sciences for the Developing World (TWAS), Trieste – Small Things and Big Changes in the Developing World (subscription required). The article makes clear just how energetically and effectively some developing countries are pursuing nanotechnology. But, the article adds, “On the downside, there is a disturbing emergence of a South-South gap in capabilities between scientifically proficient countries (Brazil, China, India, and Mexico, for example) and scientifically lagging countries, many of which are located in sub-Saharan Africa and in the Islamic world”.

    The big story, is of course, China. The same issue of Science has a very bullish article by Chunli Bai, Executive VP of the Chinese Academy of Sciences in Beijing – Ascent of Nanoscience in China (subscription required), which highlights both the investments going into nanoscience and the results in terms of scientific outputs, which have already placed China into the first rank of nanoscience nations (for example, on some measures their output has already surpassed the UK). But other countries, like India, Mexico, Brazil and South Africa, are making significant investments. Hassan’s article quotes the Nigerian Minister of Science and Technology for the rationale: “developing countries will not catch up with developed countries by investing in existing technologies alone. [In order] to compete successfully in global science today, a portion of the science and technology budget of every country must focus on cutting-edge science and technologies”.

    The danger that Hassan sees is that the research goals of the developing nations that are successful in developing nanotechnology will become too closely aligned with those of the rich countries (i.e. creating lucrative goods for consumer markets) rather than focusing on the those issues that are particularly important for the developing world.

    All things begin & end in Albions ancient Druid rocky shore

    Soft Machines is taking a short break – I’m going to the seaside with my family for a week and will be away from internet contact. My apologies in advance for any comment spam that gets through the filters.

    I always like to be on vacation on July 4th; it’s both my wedding anniversary and my son’s birthday. For any readers who might have any other reason to celebrate that day, have a happy holiday.