Inner Space

28 February 2007 (Last Updated February 28th, 2007 18:30)

Nanotechnology is expected to have a massive impact on the way diseases are detected and patients are treated. Huw Kidwell asks three experts in the field to assess its potential.

Inner Space

Nanotechnology is a phenomenon poised to change our lives. One of the
largest fields for nanotechnology use is the medical device market. Over the
next five to six years, technologies are set to become available that will have
a massive impact across the whole market, changing it forever.

But forget preconceived notions born of a misspent youth reading science
fiction, as the truth about nanotechnology is not all miniature robots
rebuilding and restructuring a patient from the inside out. The truth is that
nanotechnology will allow diseases to be detected earlier – at the level
of one or two cells – and thus enable earlier treatment and a much
improved prognosis for the patient.

To accomplish this, along with even greater possibilities, a deeper
understanding of how the human body works is still required, as a sensor or a
nanoscale device cannot be used to detect or treat a condition if you
don’t know what you are looking for. So, although nanotechnology in
medicine is developing rapidly, the quantum leap whereby nanoscale devices take
over vital functions of the body may still be a long way off.

"We are creatures whose characteristics are defined at the nanoscale − and likewise the characteristics of disease are defined at the nanoscale."

Currently, nanotechnology in medicine is all about the detection and
treatment of disease at a microscopic level and not about enhancement of the
function of the human body, although this may be on the agenda in the
future.

DEFINING NANOTECHNOLOGY

It is important to understand exactly what nanotechnology is and what it is
possible to achieve through its application. Ottilia Saxl, CEO at the Institute
of Nanotechnology, based at the University of Stirling in Scotland, says: "When
people talk about nanotechnology they always try and define it in terms that
are sometimes quite hard to relate to; but what is easier to relate to is the
fact that we are creatures whose characteristics are defined at the nanoscale
– and likewise the characteristics of disease are defined at the
nanoscale.

"So, as time goes on, if we have better tools to enable us to understand
more about the molecular basis of diseases and how they manifest themselves,
the more we will understand. We can work at the nanoscale to manipulate atoms
and molecules – [discovering] how to cure diseases earlier... and we can
create new devices and therapies that are more body friendly and compatible and
give a better solution to disease.

"It has always been a kind of Holy Grail to detect disease as early as
possible – the later disease is detected the more difficult it is to
cure, the more painful for the patient and the more long-term and expensive it
is. If you can detect disease at the level of a cell or two, you can treat it
much more effectively, so one of the techniques for nanotechnology is in
imaging, which is critical to all of this. Imaging companies are looking at not
only imaging the body but also how accurately and how early conditions can be
detected."

A disease site has a different chemistry to other tissues and a chemical
marker (functionalised molecule) can be tailored to interact with a specific
disease chemistry and cause an actuator or reaction to indicate the disease,
such as fluorescence. The contrast marker can also be designed to carry a
therapeutic drug at the same time as the diagnosis and be triggered by various
means (such as ultrasonics, magnetic field) to release the drug at the disease
site as treatment – this is called theranostics (identification/diagnosis
and treatment).

"Another approach to diagnostics is to have a diagnostic tool, which would
consist of an array of sensors able to carry out over 100 different tests
incorporated in a single nanoscale device, inside or outside the body, which
could monitor the levels of enzymes and hormones and other physiological and
biochemical parameters to detect a disease condition," adds Saxl.

"We have established that nanoscale devices can be used to target disease
and deliver drugs but another active area of research is in organ regeneration
where a nanotechnology scaffold structure, containing artificial capillaries
and ducts (also nanodevices) can be used to grow a new organ from a piece of
the patient’s own tissue. Obviously this would mean no problems with
rejection."

Finally, there is the development of artificial retinas (highly
sophisticated sensor arrays) and cochlear implants using micro electro
mechanical (MEMs) devices. "These will be some of the most sophisticated
devices to integrate with the human body ever produced and will have the power
to change people’s lives immeasurably," says Saxl. These are exciting
times and over the next ten to 15 years nanotechnology will develop, mature and
be a major driving force in the area of medical devices.

MEDICAL DEVICE MARKET

What is the current state of the market? Are there any devices incorporating
nanotechnology? Abhishek Dutta, a research analyst with Frost and Sullivan,
puts the market into perspective: "At present, nanotechnology for medical
devices has not yet evolved to an extent that there are many on the market. The
major influx of nanotechnology-based devices in the marketplace is expected
within five to six years. It will be huge and will be a major force in many
medical fields, indeed, there are so many companies researching imaging
technology and MEMs that the magnitude of nanotechnology will surpass anything
seen previously.

"Of course there are silver (antimicrobial), barium sulphate and titanium
oxide nanoparticles incorporated into artificial joint and implant surfaces,
which have been used because of their excellent antibacterial properties and
their ability to act as a key for bone cement," adds Dutta. When the technology
has evolved for use inside the human body there will be biocompatibility issues
to be addressed and this will lead to regulatory considerations – another
hurdle for nanotechnology to overcome.

"This may well be very important for quantum dot devices used inside the
body as sensors, contrast agents and test arrays, as they must be used with a
suitable coating," says Dutta. Some of the materials they contain (such as
cadmium and tellurium) may be toxic if they are used as "naked" quantum dots;
therefore, the integrity of the coating is an important regulatory issue.

"Nanotechnology will have a huge impact on many medical markets,
particularly the pharmaceutical market. In pharmaceuticals, nanotechnology will
be able to provide new drug delivery technology (nano spheres or nano
capsules). Much research is being carried out at the moment on nano coatings;
this type of technology could well be used for applications such as insulin
delivery or even gene therapy."

Nanotechnology is going to make a lot of things possible, but we must be
realistic if we want nanotechnology to do something for us. We have to
understand what we are trying to achieve and how we want to achieve it –
so rather than a "magic bullet", nanotechnology is an extremely exciting new
technology, the limits of which have not yet been established.

FUTURE OPPORTUNITIES

Nanotechnology is a fascinating subject area, and when considered in
conjunction with medical devices the potential for future applications appears
very exciting indeed. But what is the future potential in this area? Where will
nanotechnology propel the medical device market in ten to 15 years?

An expert in the field of nanotechnology, Dr Leonard Fass, director of
academic relations, GE Healthcare, is perfectly placed to answer these
questions. ‘If we can examine the field of drug delivery first (with
devices such as liposomes, nano spheres and nano capsules), these can be used
to deliver cocktails of drugs to specific areas and also contrast agents so
that the effects of the drugs can be seen in real time.

Drug delivery systems can also be controlled very specifically and
accurately by external forces such as magnetic fields or ultrasound or combined
with nano particles to treat small areas of tissue.

"One example of this would be in a patient with deep vein thrombosis coming
from Australia on a plane. There may be systems in place in the future where
treatment will be provided in situ. In this case, there would be ultrasound
transducers (capacitor micro machine ultrasound transducers) so small they
could be placed on the patient’s skin and operated remotely by a doctor
using satellite communication. A thrombolytic agent consisting of nano
particles could already be in place throughout the body, and just a specific
area would be activated (without risk of haemorrhage in other areas) to treat
(dissolve) the thrombosis."

Miniaturisation is one of the key areas for nanotechnology in medical
devices, where sensor devices can be made small enough to go into the body to
measure functions such as heart rate or glucose levels.

"There are warnings that nanotechnology could be risky, but these seem unfounded, as validation systems are being put into place."

"Remote sensing will be a very important area," adds Fass, especially as
most patients won’t need to be in hospital – 80% of patients do not
need to be there and could be monitored by physicians from their own homes.
Sensors are being made so small that patients can wear them on clothes and the
data can be transmitted by a mobile phone ...This is an area where
nanotechnology will be very important. The power requirements of future
nanotechnology medical devices inside the body may also be satisfied by the
incorporation of glucose fuel cells.

"Microfluidics is another important area in medical devices and this
involves miniature polymer or glass "slides" with channels of only a few
microns thick that could contain as little as 1,000pl of solution. These
devices can be used for analysis and separation of components (proteins, DNA)
in liquids, and the preparation of micro quantities of contrast/ tracer agents
in situ for new imaging techniques such as positron emission tomography (PET)
to examine, for instance, the Amyloid ß plaque in the brain in
Alzheimer’s disease.

"Microfluidics can also be used in phase zero microdosing (recently approved
by the FDA) to test the kinetics and physical effects of new drugs at a very
early stage in a human model, thereby making animal testing less necessary.
Microfluidic devices may also be attached to DNA aptamers and can act as
antibodies to DNA or proteins; these systems are being developed so they can
act at concentrations as low as 10-18 [the atom/molecular level for very high
sensitivity detection]."

Nanotechnology in medical devices is a rapidly expanding area. For the first
time, devices and sensors will be small enough to go into the body to diagnose
and treat disease conditions at a cellular level and even through the
blood-brain barrier to examine neurological conditions. As ever there are
warnings that nanotechnology could be risky and may harm the environment but
these seem unfounded, as validation systems are being put into place in a
similar way to those used for pharmaceuticals.

The benefits of nanotechnology in medicine far outweigh the risks. Recent
studies by Qinetiq have shown that in nanotechnology manufacturing cleanroom
areas the air has 25 nano particles per cubic centimetre while in a busy London
street there are one million particles per cubic centimetre.

Humans have been constantly exposed to nano particles for a long time
without any harmful effects, and the public is excited about the opportunities
nanotechnology will offer in the years to come. A recent study by Rice
University in Texas, University College London and the London Business School
concluded that "US consumers are willing to use specific nano-containing
products, even if there are health and safety risks, when the potential
benefits are high".

Nanotechnology is set to shape the future of medical devices and the medical
industry in general.