[Science Magazine 11 March 2011, Creating Favorable Geometries for Directing Organic Photoreactions in Alkanethiolate Monolayers]

Nanoballoons for cancer therapy – Nanomedicine | There are many ways researchers are looking into using nanostructures (such as nanotubes, nanowires, nanoparticles) to deliver medicine to very specific targets (often cancerous tissue). One of the more promising was developed by a research team at Princess Margaret Hospital (Ontario, Canada) that uses what might be called nanoballoons, structures no bigger than 1/100,000 the width of a human hair that look like a colorful balloon. The nanoballoon is created by combining chlorophyll and a lipid (fat) and distinguishes itself from other nanoparticle forms in being biochemically safe (non-toxic) and usable in several different techniques: Photothermal therapy to heat cancer cells until they are killed, photoacoustic therapy to find and remove cells, and as a container to hold chemotherapy drugs for precise delivery to a cancerous area. The research has prototyped the nanoballoon techniques but much more work needs to be done to show that this particular approach can be used clinically.

[Nature Materials 20 March 2011, Porphysome nanovesicles generated by porphyrin bilayers for use as multimodal biophotonic contrast agents]

White dwarf stars: A good place to look for Earth-like planets – Exogenous Life | Stars come in many sizes and conditions, although ‘enormous’ and ‘very hot’ sort of cover the lot. However, there are also a number of ‘colored’ star types known collectively as ‘dwarfs’ – red (low mass), yellow (like our Sun), white (a dying star), black (a white dwarf emitting no visible light) and brown (smaller than a star with minimal heat). In general these stars are less energetic (including less explosive and violent), a condition that favors retaining planets in the ‘Goldilocks zone’ – orbits that are close enough to the star to get sufficient heat, but not in danger of being destroyed by emissions from the star. This is the zone Earth occupies and it is presumed that similar earth-like planets might exist. The implication is that such planets could harbor life. A new paper by Eric Agol at the University of Washington (Seattle, USA) suggests that white dwarfs would be a good place to look for these planets. Because white dwarfs are small and relatively cool, planets can exist much closer to the star and that should make them easier to spot with current telescope technology. There are approximately 20,000 white dwarfs relatively close to Earth.

[Astrophysics Journal Letters 5 April 2011, Eurekalert]

A primordial soup revisited – Origin of Life | In 1953 Stanley Miller began a series of experiments designed to explore the idea of a primordial soup, the mixture of chemical ingredients that could lead to the origin of life on Earth. His first research used a simple mixture of water, methane, ammonia and hydrogen – common chemicals in asteroid and meteor bodies – through which was passed an electric current. The results, which were startling at the time, were a number of complex amino acids, the building blocks of life. Miller continued his research through 1958 but he died in 2007 leaving his notes and experiments unfinished. One of Miller’s former students, Jeffrey Bada has picked up the research, using tools and instruments more sophisticated than those available to Miller. In one new experiment, based on Miller’s notes, hydrogen sulphide (the smell of rotten eggs) was added to the mix. The results included an astonishing 23 amino acids, four amines and seven organo-sulphur compounds. Keep in mind these are pre-biotic materials that are considered necessary for organic life but have not yet been combined in a way to actually create life. What that process was, as yet, is unknown. Nevertheless, the results indicate that from some very common chemical substances and a simple electrical discharge the basic organic components of life can be made. This knowledge increases the probability that life could have formed many places in the universe.

[PNAS 21 March 2011, Primordial synthesis of amines and amino acids in a 1958 Miller H2S-rich spark discharge experiment]

[BioMaterials, Volume 32, Issue 13, May 2011, Pages 3481-3486, Co-encapsulation of magnetic nanoparticles and doxorubicin into biodegradable microcarriers for deep tissue targeting by vascular MRI navigation]

W.H.O. response to pandemic that wasn’t is criticized – Pandemics | The H1N1 “Swine Flu” pandemic of 2009 fizzled. Thank goodness. The World Health Organization (W.H.O.) received a lot of criticism for promoting a worldwide pandemic management and vaccination program, in large part because the H1N1 virus (a cross of pig, human and avian genetics) turned out to be no more virulent than ‘normal’ flu. Now a follow-up study of the H1N1 episode, at the behest of W.H.O., finds that the world was lucky: W.H.O. and its member countries, particularly those involved with the new International Health Regulations (IHR) were not and are not ready for a seriously dangerous pandemic. The report, which will be officially released later this year, largely clears W.H.O. for its timing in declaring an emergency and for charges of being influenced by large drug companies, but it finds fault with the uncertainty of W.H.O. categorization of the outbreak and with the ability of W.H.O. to manage the IHR agreements between countries. Consider the 2009 H1N1 outbreak a dry-run, a chance to critique and improve the world’s response capability. The next outbreak may not be so meek.

[New York Times, 10 March 2011, Response of W.H.O. to swine flu is criticized]

Title – Photonics | Perhaps you’ve heard that quantum computers are ‘just around the bend’ so to speak. It could be a long curve. Nevertheless, by the time quantum computers become real it would be a good idea to hook them to quantum networks. To that end researchers at Northwestern University (Illinois, USA) have demonstrated a network switching device (a switch changes the route of network information) that can handle quantum bits (particles of light involved in the quantum effect called entanglement) without losing the embedded information. In this case the quantum bit (qubit) is a photon, which is emitted by a device the researchers created called a Entangled Photon Source. Pairs of entangled photons (entangled meaning that both photons are linked by a quantum relationship) are transmitted via optic fiber through the new photonic switch – without losing their entanglement. This quantum communication is many times faster than existing digital systems and only needs quantum computers to become the high powered computing of the future – a few years down the line.

[Physical Review Letters, 1 February 2011, Ultrafast switching of photonic entanglement]

Synthetic biology: Replacement urinary tubes – Synthetic Biology | The first human replacement of damaged urinary tubes (urethra) with synthetically produced tissue may not seem like a glamorous piece of synthetic biology, and it isn’t – and that’s the point. Researchers are now developing ‘artificial’ tissue replacements for a number of organs, many of them sort of ‘routine’ but nonetheless vital for the person whose native equipment is defective. The researchers at Wake Forest Baptist Medical Center (USA) have progressed to human trials, in this case, replacing long segments of urinary tubes in five boys. Creating these tubes with tissue grafts has a high failure rate (around 50%). The synthetic tubes are grown from the patient’s own cells and do not provoke a tissue rejection. They are more easily controlled for size, shape and consistency, which should result in a much lower failure rate. Determining that rate will be part of the next phase of human testing.

[Lancet, 8 March 2011 Tissue-engineered autologous urethras for patients who need reconstruction: an observational study]

Nanotiles make a programmable processor – Computer Power | Using nanotechnology components for computing is one of the most active of all research areas. Much of the activity concerns using nanotubes and other carbon-based nano-shapes for digital switches (for memory and logic components). In this case engineers and scientists at Harvard University and MITRE Corporation (USA) have created nanowire tiles that can be arranged in the world’s first programmable nanoprocessor. Charles Lieber and colleagues use carbon nanowires that are arranged by some breakthrough processing technology to form circuitry on a ‘tile’ (a substrate material). This is analogous to printing circuits on silicon chips of traditional computing, but here the tiles are at the nano scale. They are so tiny that the power consumption is negligible and each circuit can retain a charge (like computer memory), yet stacked together the tiles form complex circuits that can perform logic and arithmetic. This combination of non-volatile memory and programmable circuits – at the nanoscale – constitutes a new and potentially important approach to developing computers ‘from the bottom up.’ That is, instead of designing complete circuits and imprinting them on a semiconductor, the processors circuits are built piece by piece (tile by tile). The end product will be, in the not too distant future, computer processors no bigger than the head of a pin (on which the angels will dance).

[Nature, 9 February 2011, Programmable nanowire circuits for processors]

Clean Transport – VW Hybrid achieves about 280 miles per gallon | There’s nothing like competitive pressure among engineers. Make a car that gets better mileage (sorry for the Americanism) than anybody else. It’s a wonderful competition for all concerned. In this case it is the wizards at Volkswagen (Germany) that developed a hybrid (electrical/internal combustion) vehicle that can achieve 100km per liter of fuel.
[The Engineer Blog, Hybrid concept car achieves record fuel economy]

Clean Transport – Split-cycle engine for 50% better fuel economy | The Scuderi Group, specialists in engine design, have announced a new angle on the split-cycle (4 cylinder, split into two pairs) engine that uses a compressor to capture engine heat-energy and achieve much greater fuel economy than similar engine designs.
[Popular Science, New Split-Cycle Engine Design Shown To Improve Fuel Economy by 50 Percent]

Neuroscience – The brain dumps data really fast | Here’s the punch line from the Max Planck Institute for Dynamics and Self- Organization (Göttingen, Germany): “Due to the high deletion rate [one bit of data per neuron second], information about sensory input signals can only be maintained for a few spikes. These new findings indicate that the dynamics of the cerebral cortex are specifically tailored to the processing of brief snapshots of the outside world.”
[Max Planck Institute, Out of mind in a matter of seconds]

Neuroscience – The brain reconnects as it grows | Scientists at the Scripps Research Institute (USA) are attempting to map all of the neural connections in the animal brain have discovered that these connections reform (change their switching pattern, so to speak) as the brain develops with age. The picture of the connectome, as they call it, provided some important surprises: Neurons actively seek out partner neurons; the seeking, however, doesn’t go to the neuron but instead to the axonal boutons that already have connections; it is important for future studies to not only consider how neurons grow, but also how other neurons are eliminated during the process.
[EurekAlert, Scripps Research study shows map of brain connectivity changes during development]

Nanomedicine – Nanoparticles created by peptides and growth-factor speed healing | A combination of keratinocyte growth factor and elastin-like peptides were show to self-assemble (fuse) into a nanoparticle that can be used to treat deep-seated wounds more effectively and less expensively than using growth-factor alone.
[EurekAlert, Growth-factor-containing nanoparticles accelerate healing of chronic wounds]

Synthetic Biology – Growing human liver tissue for transplants | Researchers at the University Medical Center (Hamburg, Germany) have successfully grown human liver cells on a synthetic scaffolding (supporting structure) that can be used for replacement tissue in damaged or failing livers. The results are now undergoing confirmation.
[EurekAlert, Scientists grow human liver tissue to be used for transplantation]

Even in English the fluffy balls of finely spun sugar have different names: Cotton candy (US), candyfloss (UK), fairy floss (Australia), but world-wide it’s a technique for creating airy, often colored confections. Why not apply this same technique for nanofibers? Why not indeed, thought a research team at Harvard School of Engineering and Applied Sciences (USA).

The most common way of making nanofibers is to use a high voltage electric charge in droplets of the basic material (typically a polymer plastic). At a high enough charge the droplet erupts into a thin (nanoscale) stream and whipped by electrostatic repulsion into a fiber. The process, called electrospinning, works but is difficult to control and tends to produce uneven results.

The Harvard solution uses a rotary jet spinner, very similar in technique to that used for creating cotton candy. It’s a mechanical process and doesn’t require the use of high voltage equipment. Better still, it’s much more easily controlled.

Like the production of cotton candy, the use of a jet nozzle (density and diameter control) and a spinning collector (uniformity, shape and diameter control) can work with a range of natural and synthetic polymers to produce a high degree of flexibility in the diameter of the fibers and their alignment. The texture of the fibers can also be varied from smooth to beaded. There is even some ability to produce artificial structures, something like a three-dimensional weave that can be used as the basis of body tissue. This ‘shaping’ aspect of the technique has drawn the attention of medical researchers, who are using the nanofibers as tissue scaffolding (superstructure) in experiments with growing heart muscle from rats.

As co-author of the paper published in the May 24 edition of Nano Letters, Kit Parker (Thomas D. Cabot Associate Professor of Applied Science) put it:

“I was visiting the Society of Laproscopic Surgeons a couple of years ago to look at the equipment demos and it dawned on me that we needed to develop techniques to miniaturize scaffold production so we could do it in vivo. Our finding is the first step,” explains Parker. “The initial testing suggests that our technique is incredibly versatile for both research and everyday applications. As rotary jet spinning does not require high voltage, it really brings nanofiber fabrication to everyone.”

[Source: Nanotechnology Today]

Well, perhaps not everyone can do it, but the technique has many obvious advantages. Nanofibers, like other nano-shapes such as nanotubes and nanoparticles are proving to have a wide variety of applications. What will make these applications commonplace will be the production techniques that provide the right kind of control and the ability to ‘scale’ – produce at higher volume.

The key to antibodies is the ability of an antibody molecule to have just the right configuration or shape to receive (or imprint) the target. Most invading material, bacteria or virus, has protein structures with distinctive shapes. Think of it like Lego structures with turns, L’s, arms, corners, and pockets. Antibodies have corresponding shapes that can bind (accept or receive) specific bacteria or virus shapes, after which their chemical components go to work to destroy the invader. Artificial antibodies will have to have this same capability.

The idea of using plastic (polymers) for artificial antibodies goes back many years when scientists were becoming disenchanted with using natural proteins to simulate antibodies. The natural protein structures were (and are) difficult to manipulate, not very robust, and unreliable to load with various kinds of reactive chemicals. By contrast plastic structures could be cheap, easily manipulated, quite robust within the body (that is, lasting long enough to do the job), and were generally not affected by the types of medicine loaded into them.

The ‘plastic’ of this kind falls into the category of nanomedicine because typically the polymer shapes are themselves molecules of only a few nanometers (on the order of a few 1/100,000ths of the thickness of human hair) in size. It has taken scientists a long time to master the production techniques for making polymer shapes with exactly the right configuration to attack a specific antigen.

The case in point is work done by pioneers in this field, Yu Hoshino and Kenneth Shea (University of California, Irvine, USA) in collaboration with researchers at the University of Shizuoka (Japan) and Stanford University (USA). As published in April’s issue of the Journal of the American Chemical Society, the team concentrated on the antigen melittin, a toxin found in bee stings that can be a potent (even fatal) inflammatory and cellular disruption agent. In humans, the effects of bee stings and melittin can occur long before the body can produce enough appropriate antibodies, so having an effective artificial antibody could save many lives.

The researchers used chains of polymer molecules to manufacture a shape with exactly the right indentations (“craters”) to accept the shape of the melittin toxin. The tiny, molecular, artificial antibodies were then injected into mice close to dying from a dose of melittin. The effect was strong enough to not only bind to the melittin, but also to reduce its potency and thereby increasing the probability of survival for many mice. This was a first, a live test of the plastic antibodies. As Kenneth Shea put it:

“This opens the door to serious consideration for these nanoparticles in all applications where antibodies are used,” Shea said in a prepared statement, suggesting the technique could be used to generate plastic antibodies tailored to fight any number of troublesome antigens.

[Source: Scientific American]

Perhaps they can, but a trial in mice doesn’t tell the whole story. This approach is long years away from human trials and from allaying a concern over injecting nanoparticles for such critical medicine. Nevertheless, of such steps are science made, and this is one to keep an eye on because the impact of artificial antibodies could be considerable.

The nanosponge is about the size of a virus with a ‘backbone’ (a scaffold structure) of naturally degradable polyester (not the stuff in suits). The long(ish) polyester strands are mixed with small molecules that have an affinity for certain portions of the polyester. They ‘cross link’ segments of the polyester to form a spherical shape that has many pockets (or cavities) where drugs can be stored. You might wonder about polyester; this particular version is predictably biodegradable, which means that when it breaks up in the body, the drug contained can be released on a known schedule. Better still; the nanosponge can be engineered to be of specific size and to release drugs over time – not just in the ‘burst’ mode common with other delivery methods. The engineering capacity of nanosponge is due to the relatively simple chemistry of its polyesters and linking material (peptides); compared to many other nanoscale drug delivery systems, nanosponge should be able to scale (e.g. ramp up to commercial production levels) without requiring unusual equipment or procedures.

Nanosponge is water soluble. This does not mean the molecules chemically break up in water, but it means that nanosponge particles can mix with water and use it as a transport fluid, for example to be injected. Most other forms of nanoparticle delivery systems must use various chemical transports (for example, adjuvant reagent), which may have side effects.

So…in theory nanosponge has several advantages over other delivery methods. It has been used in a successful single-injection test, delivering the drug paclitaxel (generic Taxol) to mice with glioma (a fast acting brain cancer) and cells with human breast cancer. The next tests will be a series of injections against whole tumors. In parallel to these tests, the approach must also be evaluated for toxicity. Like all nanomedical materials nanosponge will need lengthy phased trials, which means that commercial availability is still years away. It’s getting attention now because of its fundamental properties – particularly the engineering and production simplicity.

The other major advantage of Harth’s system is the simple chemistry required. The researchers have developed simple, high-yield “click chemistry” methods for making the nanosponge particles and for attaching the linkers, which are made from peptides, relatively small biological molecules built by linking amino acids.

“Many other drug delivery systems require complicated chemistry that will be difficult to scale up for commercial production, but we have continually kept this in mind,” Harth says.

[Source: Futurity]

“You could imagine the spider carrying a drug and bonding to a two-dimensional surface like a cell membrane, finding the receptors and, depending on the local environment,” adds Yan, “triggering the activation of this drug.”

Such applications, while intriguing, are decades or more away. “This may be 100 years in the future,” Stojanovic says. “We’re so far from that right now.”

[Source: EurekAlert]

In other words: ‘What we’re doing is so basic – baby steps – that we’re a long, long way from doing something with real world application.’ Yet, it’s exciting or perhaps a tad creepy that these scientists are talking about their creation of a molecular robot – that’s correct – a moving, autonomous robot no bigger than a few molecules across, which they dubbed a ‘spider’. Moreover, for the first time, this nanorobot is, in a sense, programmable.

To highlight just how much work a ‘baby step’ (a.k.a. pioneering research) requires, here’s a partial list of the collaborators:

Milan N. Stojanovic, a faculty member in the Division of Experimental Therapeutics at Columbia University, led the project and teamed up with Winfree and Hao Yan, professor of chemistry and biochemistry at Arizona State University and an expert in DNA nanotechnology, and with Nils G. Walter, professor of chemistry and director of the Single Molecule Analysis in Real-Time (SMART) Center at the University of Michigan in Ann Arbor, for what became a modern-day self-assembly of like-minded scientists with the complementary areas of expertise needed to tackle a tough problem.

What made this research ‘tough’ was the goal of making a nanorobot in some way programmable. There have been other projects resulting in molecular robots that move, and projects with nanorobots that ‘do something.’ But these actions were all ‘one-off,’ some simple motion or activity performed a few times without variation. This project wanted a nanorobot that could actually take instructions; simple instructions such as go, stop, turn, forward, backward.

The work started with building a molecular robot 4 nanometers in diameter. That’s a robot about the size of 4/100,000ths of the end of a human hair. That’s microscopic, of course, and requiring very high powered electron microscopes to assemble the component molecules and do the initial fabrication. They used a common protein (streptavidin) because it has four symmetrically ordered ‘pockets’ for binding the chemical biotin. This is where the ‘legs’ of a biotin-labeled strands of DNA were attached. (Making an anomalous four-legged spider.) Three of these legs were made of enzymatic DNA, a DNA that can cut other sequences of DNA. The fourth leg was a ‘start strand’ that would hold the robot onto the origami track.

The origami track was key to this research. DNA origami has a chemical composition that allows the DNA structure to be precisely folded into a very wide range of shapes. It’s a mixture of long DNA strands, and short DNA strands that, in effect, staple the long strands into the various shapes. In this case, the origami DNA was a rectangle 2 nanometers thick and roughly 100 nanometers on each side (like a patch). To this origami shape, the researchers attached single-stranded DNA molecules (oligonucleotides) at the ends of each short DNA staple. These became the ‘code’ or ‘cues’ to be read by the moving robot as instructions (start, turn right, stop, etc.).

The origami shapes, placed in alignment, became the track along which the robot would move. It’s enzymatic legs would be drawn to the single-stranded DNA molecules where it binds to them, and then cuts them – freeing itself to move to the next shape in the track. The robot stops when it encounters an origami shape to which it binds but cannot cut. Using atomic force microscopes and single-molecule fluorescence microscopy, the scientists were able to watch the progress of their robot as it made multi-step movements along the path of origami shapes, and directing it to make specific moves – which in a sense were its programming.

“Monitoring this at a single molecule level is very challenging,” says Walter. “This is why we have an interdisciplinary, multi-institute operation. We have people constructing the spider, characterizing the basic spider. We have the capability to assemble the track, and analyze the system with single-molecule imaging. That’s the technical challenge.” The scientific challenges for the future, Yan says, “are how to make the spider walk faster and how to make it more programmable, so it can follow many commands on the track and make more decisions, implementing logical behavior.”

“In the current system,” says Stojanovic, “interactions are restricted to the walker and the environment. Our next step is to add a second walker, so the walkers can communicate with each other directly and via the environment. The spiders will work together to accomplish a goal.” Adds Winfree, “The key is how to learn to program higher-level behaviors through lower-level interactions.”

Note the forward-looking language. These scientists are well aware that their work is primitive. They wish they could go faster; make the robot learn more; but working at the molecular level is very difficult. Everything is invisible in the normal sense. Everything is very small and cramped – there is no room, for example, for the robot to carry its own instructions or data. That has to be external to the molecules that make up the robot, which is why the origami DNA track was created.

The nanoprojections puncture the top layer of skin to reach specific cells in the epidermis called Langerhans cells. These are the first skin members of the body’s immune system. They pick up the antigen from the nanopatch and move it to the lymph nodes, the hubs of the immune system. Once in the lymph nodes, the Langerhans cells mature and make the antigen available to another worker in the immune system, the T-cell.

T-cells are studded with receptors – tiny protuberances designed to pick up the molecular configuration of antigens in this case presented by Langerhans cells. The T-cells come in many different types, and among the types are sometimes differentiated to be sensitive to only one type of antigen. When it comes in contact with that antigen, it binds it to a receptor and from then on ‘remembers’ that type of antigen. The T-cells work together with B-cells to provide an attack on specific antigens whenever they are detected in the body. This is the basis of immunization.

The nanopatch approach is designed to directly affect T-cell immunization with a huge advantage in being able to ‘educate’ the T-cells about a particular antigen without the need for actually suffering the disease. Its effect, in some cases, is stronger than needle injected vaccine especially for infections such as HIV and malaria. The nanopatch is generally inexpensive to manufacture and typically requires much less vaccine.

It should be noted that the nanopatch is still undergoing trials in mice, which means that application to humans is still down the road, and commercial availability in perhaps several years. Nevertheless, a very promising technology.

Crichton, M., Ansaldo, A., Chen, X., Prow, T., Fernando, G., & Kendall, M. (2010). The effect of strain rate on the precision of penetration of short densely-packed microprojection array patches coated with vaccine Biomaterials, 31 (16), 4562-4572 DOI: 10.1016/j.biomaterials.2010.02.022

[Source: A Schooner of Science Blog]

The approach begins with the work of the 2006 Nobelists in Medicine, Andrew Fire and Craig Mello, demonstrating a new method to prevent a cell from producing a specific protein. They accomplished this by attaching a double stranded small interfering RNA (siRNA) to the RNA of cells. This turned off a specific gene through what they called RNA interference (RNAi).

The importance of this approach for cancer research was that it showed how to attack a cancerous cell not through its (abnormal) proteins, which are difficult to access with a treatment, and instead attack the messenger – the RNA. RNA in several forms has a primary task within cells of transferring the instructions from DNA in the nucleus to the protein manufacturing components outside of the nucleus (the ribosomes). By attaching the right siRNA to the RNA of a cancerous cell, it turns off the production of certain proteins.

This approach, in theory, was very promising, but there were difficulties, the most important being that siRNA didn’t survive delivery into a cell. Here is where nanotechnology provided the solution. Nanoparticles – by nature very small (1/100,000th of the width of a hair) – could easily penetrate the cell wall (membrane). By attaching siRNA molecules to nanoparticles, the molecules survived crossing the cell membrane and then could deliver the siRNA to the targeted mRNA. The composition of the siRNA and its nanoparticle transportation is a proprietary process (now commercially licensed), but involves a self-assembling polymer (jargon for molecular chains that will automatically bond into a predesigned form).

Phase I clinical trials, which in the pharmacological trade means testing for dosage levels in human applications, commenced in 2008 and is now being reported in the journal Nature. The trials demonstrated that the nanoparticles could find the targeted cells (in tumors), penetrate the cell membranes, and release their cargo of siRNA. They were also able to show that higher levels of nanoparticles (higher dosage) resulted in more nanoparticles in tumor cells. More importantly, analysis of the cells indicated that the siRNA had done its job – broken up the cell’s RNA at the targeted location. For the first time in homo vivo it could be shown that production of a specific protein could be blocked by the introduction of a protein specific siRNA. The RNA interference effect worked.

“There are many cancer targets that can be efficiently blocked in the laboratory using siRNA, but blocking them in the clinic has been elusive,” says Antoni Ribas, associate professor of medicine and surgery at UCLA’s Jonsson Comprehensive Cancer Center. “This is because many of these targets are not amenable to be blocked by traditionally designed anti-cancer drugs. This research provides the first evidence that what works in the lab could help patients in the future by the specific delivery of siRNA using targeted nanoparticles. We can start thinking about targeting the untargetable.”

[Source: EurekAlert]

These were Phase I trials with one target protein. This is a long way from finding a spectrum of protein targets, or passing other phases of clinical trials. It will be years before this anti-cancer approach will be approved for general use – but – this is promising by almost any standard.

It’s more than a disinfectant and hair bleach, that’s for sure. It’s an organic compound (H2O2) found in all organisms that use oxygen for metabolism. It has been known for some time that hydrogen peroxide can damage cells and DNA, but recently it’s also become known that it is used as a signaling molecule for the stimulation of cell growth. Signaling molecules are like messengers; they get sent when something needs to happen – in this case, the chemistry of cell metabolism comes to the point where cell growth or division is ‘necessary’ and it generates hydrogen peroxide molecules. These molecules, in turn, work with a common growth factor called EGF (Epidermal Growth Factor), which binds to its receptor on the outer membrane of cells (EGFR). This induces cells to grow or divide. In some way (still unknown) hydrogen peroxide amplifies the EGFR signal.

The hydrogen peroxide molecule is very small and typically does not leave the vicinity of a single cell – hence the need for detection at the level of one molecule and one cell.

The sensor constructed at MIT is a film of carbon nanotubes embedded in collagen (a gel-like protein that makes up about 20-35% of animal tissue). Cells are grown on the surface of this nanotube ‘carpet’ and the collagen attracts the hydrogen peroxide produced by the cells. To get to the collagen, however, the hydrogen peroxide must enter a nanotube. The nanotubes have been treated with a fluorescent material that reacts in the presence of hydrogen peroxide. The nanotubes ‘flicker’ when reacting, which can be recorded and counted – thus providing an accurate count of the production of hydrogen peroxide, one molecule at a time.

This has a variety of uses…

The team also found that in skin cancer cells, believed to have overactive EGFR activity, the hydrogen peroxide flux was 10 times greater than in normal cells. Because of that dramatic difference, Strano believes this technology could be useful in building diagnostic devices for some types of cancer.”You could envision a small handheld device, for example, which your doctor could point at some tissue in a minimally invasive manner and tell if this pathway is corrupted.”

Strano points out that this is the first time an array of sensors with single-molecule specificity has ever been demonstrated. He and his colleagues derived mathematically that such an array can distinguish “near field” molecular generation from that which takes place far from the sensor surface. “Arrays of this type have the ability to distinguish, for example, if single molecules are coming from an enzyme located on the cell surface, or from deep within the cell,” says Strano.

Strano’s team is also working on carbon nanotube sensors for other molecules. The team has already successfully tested sensors for nitric oxide and ATP (the molecule that carries energy within a cell). “The list of biomolecules that we can now detect very specifically and selectively is growing rapidly,” says Strano, who also points out that the ability to detect and count single molecules sets carbon nanotubes apart from many other nanosensor platforms.

[Source: EurekAlert]

At the moment, the single molecule sensor array is more of a laboratory tool. It will be useful in pursuing the role of hydrogen peroxide in cell growth, of course; but if the approach is easily manufactured, and adaptable to other molecules – then this will become part of the ever increasing range of sensor technology.