Clinical Trial Finds Nanotube Sensor Can Monitor Cancer or Diabetes

FGF Clinical Trial Finds Nanotube Sensor Can Monitor Cancer or DiabetesNanotechnology in Medicine

Most everybody knows about a litmus test, strips of paper impregnated with dyes that turn red in the presence of acid and blue if there is a base (alkaline). It’s a kind of chemical sensor. There are many kinds of chemicals that can similarly act like a sensor, detecting the presence of other chemicals.

Some of them would work in the human body, detecting glucose (blood sugar) for example, but the problem has always been using them in a way that is effective to read but not harmful. In short, most biochemical sensors have a delivery problem.

Part of the nanotechnology revolution was the development of nanoparticles, small shapes mostly of carbon that are no more than 1/100,000th of the thickness of human hair, i.e. about 1 nanometer in size. Carbon nanotubes are the most common type of nanoparticle, and as the word “tube” indicates, these are incredibly tiny rods with hollow centers.

Using Nanotubes as a Biomarker

It occurred very early on to researchers that it might be possible to put something in the tubes – medicine, for example – and use the tubes to deliver the medicine to very small, very targeted locations in the body. That targeting and small ‘footprint’ was the big perceived advantage over administering a standard chemical, which would spread everywhere. Since the late 1990’s, there’s been a virtual avalanche of research into the medical uses of nanoparticles.

The concept behind most of it was fairly obvious, but in practice making it work has proven to be more difficult. Using carbon nanotubes as a biomarker (another term for biological sensor) in living tissue requires the need for compatibility with biological tissue (non-toxic), ability to carry molecules in a way recognized by biological systems (biochemical recognition), high fluorescence (visible to the eye or instruments) and/or the ability to transmit some kind of detectible signal (such as radiation).

The answer to most of these requirements turned out to be coatings, molecular layers of chemical that could be applied to the nanotubes. That’s the route taken by a team of researchers at the Massachusetts Institute of Technology (MIT), USA and published in the journal Nature Nanotechnology.

Developing Carbon Nanotubes  to Detect the Presence of Cancer

The starting point of their research was nitric oxide (NO), a combination of nitrogen and oxygen, which cells of the body use as a signaling mechanism. Various molecular configurations of NO can attach to cell receptors and act as triggers and depending on the concentration of NO, trigger more or less receptors – for example, in running between the immune system and the brain.

It’s been known for some time that the level of nitric oxide in the body is disturbed in the presence of cancer, which makes nitric oxide a potential biomarker for at least some types of cancer. The problem is that it’s necessary to draw a blood or tissue sample and run it through laboratory tests to find the level of nitric oxide. That is time consuming.

The MIT researchers reasoned that a carbon nanotube, with appropriate coatings, could detect the level of nitric oxide while residing in the body – in real time, so to speak. The nanotubes are naturally fluorescent (they glow under appropriate conditions) and can be made to glow more or less depending on the level of chemical in the coating. In this case, it meant developing a coating of polyethylene glycol (PEG, “antifreeze”) that responded to nitric oxide.

The PEG coating also keeps the nanotubes from clumping in the bloodstream. The researchers first made a version of their nitric oxide nanotubes that was injected and then traveled quickly through the heart and lungs into the liver, where it would concentrate into a detectable mass (a really very very tiny mass).

Using a special spectrographic instrument and in this case, an infrared laser for an energy source, the fluorescent mass in the liver could be read and analyzed.

With this coating and in the small amounts of injection, the nanotube sensor was not toxic. However, the researchers found that the liver was rather quick to eliminate the nanotubes, so they cast about for a more permanent solution.

That turned out to be embedding the nanotubes in a gel made from algae, which could be safely implanted under the skin. At least in mice, this technique would stay in place and remain active for about 400 days.

Sub-dermal Nanosensors to Detect Glucose Levels in Diabetes Patients

Realizing the versatility of the sub-dermal approach, the researchers quickly expanded the application to include sensor chemicals for glucose. Glucose is the principle form of sugar (energy source) that is distributed to all the organs of the body through the bloodstream.

The researchers are working on a way to read the nanotube sensors and convert the signal into something could, for example, activate an insulin pump. It is not an exaggeration to say there are probably several hundred research projects underway that are looking for medical applications of nanoparticles.

Not many of them will even see the pages of a scientific journal, much less be approved for medical use in an actual human being. Before the approach gets that far, it must pass through the three phases of clinical trials – and hundreds of patients. It will need to show the approach is more effective, easier to administer, safer and/or costs less than many similar products.

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