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Nanotechnology and the treatment of cancer
By Perla Astudillo
20 June 2005
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Recent successful medical trials of a cancer treatment involving
the use of nanotechnology may open up important new
avenues for the diagnosis and treatment of other cancers and diseases.
Nanotechnology is a broad term covering the building of structures
and machines on an atomic or molecular scalein
the range from 1 to 100 nanometres. A nanometre is one billionth
of a metre or about the size of 10 hydrogen atoms. The techniques
range from various chemical and biological processes used to construct
structuresin some cases atom by atomto the etching
methods used to produce computer chips.
The field of nanotechnology has over the last decade or so
been surrounded by considerable hype. Some of the visions of what
is possible in medicine conjure up the Science Fiction classic
film Fantastic Voyage where tiny submarine ships were injected
into the body and travelled through the bloodstream to eradicate
foreign bodies. The reality is more prosaic, but the potential
is nonetheless exciting.
Many of the standard radiation and drug therapies now used
to treat cancers can have serious side effects. The use of radiation
and chemicals to kill fast-growing tumour cells inevitably affects
and kills other cells in the body. Nanotechnology offers the possibility
of far more precisely localising the treatment and thus minimising
the damage to healthy tissue.
In early April, the nanotechnology company pSivida announced
the very promising results of the Phase 2 clinical trials of its
product BrachySil for patients with liver cancer.
BrachySil is a tiny structure about one-millionth of a metre
in size and made up of modified particles of silicon impregnated
with the radioactive isotope of phosphorus 32P. Unlike other radiation
treatments that involve focussing beams of radiation on tumours,
BrachySil is injected directly into the cancer using a fine gauge
needle. By using 32P, the radiation is limited to a range of just
8 millimetres, resulting in the killing of tumour cells rather
than healthy tissue.
For several years, doctors have been using a similar technique
known as brachytherapyinjecting radioisotopes directly into
tumours. The difficulty was that the injected material would not
remain in the cancer, but would over time be carried to other
parts of the body. The advantage of BrachySil is that its silicon
structures, while small, prevent the radioisotope from leaking
away.
The result is that the dose of radiation is focussed very precisely
on the tumour itself. The silicon eventually breaks down and is
excreted. 32P, which has a half-life of 14 days, eventually decomposes
to stable isotopes or is excreted. Because the treatment is localised,
the side effects are likely to be less than other forms of brachytherapy.
None have been observed to date, although the long-term impact
of the treatment is not known.
BrachySil consists of tiny pockets made up of silicon microparticles.
The pores or holes in the silicon pocket are the size of about
10 atoms. Radioactive phosphorus is bombarded into the structure.
Because of its method of delivery of radiation doses, the treatment
may well be applicable to a broader range of cancers than other
forms of brachytherapy, which is currently limited to prostate
and liver cancers.
The clinical trial of BrachySil was undertaken at the Singapore
General Hospital beginning in mid-2004. It involved eight patients
suffering from primary liver cancer (where the tumours have not
spread to a secondary site). They were given CT scans before and
after the injection of BrachySil to determine the impact on the
tumours and were monitored for possible side effects.
After 12 weeks of the treatment, smaller tumours were completely
eradicated. The most extraordinary finding, however, was that
all tumours were reduced by an average of 80 percenta result
not seen in other treatments. After the trial results were announced,
the company received a flood of inquiries and was forced to announce
on its website that testing was still in its early stages.
Worldwide, liver cancer is not one of the most prevalent cancers.
Nevertheless, more than half a million new cases are diagnosed
every yearsome 45 percent of them in China. Causes of liver
cancer include infection by parasites such as the Chinese liver
fluke. Liver cancer can also be related to hepatitis, exposure
to radiation and to the irritant Polyvinyl Chloride.
Other applications of nanotechnology
An article published in the British scientific journal Nature
in March entitled Cancer Nanotechnology: Opportunities and
Challenges provided an overview of the diverse array of
nanodevices and their possible application. These included nanovectors
to provide the targetted delivery of anticancer drugs as well
as nanowires and nanocantilever arrays
for the early detection of pre-cancerous and malignant lesions.
Many of the devices are still in the process of development,
but some are being used or, like BrachySil, are in the testing
process. The earliest known application was the use of liposomes
or small spheres that have been used to treat cancers such as
Kaposis sarcoma for about 10 years. They are now being used
in cases of breast cancer and ovarian cancer.
Nanovectors are generally made up of three basic
parts: a core; the contents which may be a specific drug or chemical
used for imaging; and a surface coating. The coating is needed
both to target cancerous tissue and to prevent the bodys
own defence mechanisms from engulfing and destroying the nanovector.
In 2003, US scientists developed a nanoshell made
up of a silica core and a thin gold metal shell modified to strongly
absorb near-infrared (NIR) light. The nanoshells were injected
into mice, which were then exposed to a safe dose of NIR radiation
causing cancer cells to die. Magnetic Resonance Imaging (MRI)
scans enabled the scientists to monitor exactly where the nanospheres
were located and thus successfully target cancer cells.
Scientists have also built nanoshells to deliver small precise
doses of drugs to tumours. It is hoped that such techniques will
be able to avoid many of the serious side effects that are associated
with current chemotherapy.
At the end of March, scientists at the Institute of Bio-engineering
and Nanotechnology in Singapore published their findings on the
use of polymer nanoparticles to deliver anti-cancer drugs directly
to diseased tissue. The results showed that the technique applied
to mice was effective in conveying the drug doxorubicin to breast
tumours. The scientists hope that clinical trials will follow
in the next five years.
The nanoparticles were tagged with biological signals to enable
them to hone in on the cancer cells. This was achieved by modifying
the particles to be sensitive to both temperature and pH. The
tumour cells, which are characteristically slightly acidic, caused
the nanosphere to deform and release the drugs at
the exact site of the cancer cells. The outer shell was also coated
with bioactive compounds to protect the particle from degradation
and digestive fluids.
Nanoparticles have also been modified to provide better cancer
detection. Researchers at Washington University School of Medicine
demonstrated that very small human melanoma tumours growing in
micethat are not discernible using a direct MRI scanwould
light up and be easily located some 30 minutes after
the mice were injected with specialised nanoparticles.
Stanford University nanotechnology expert Stephen Quake has
predicted within a decade that the diagnosis and treatment of
cancers and other diseases will be carried out automatically,
in a few seconds or minutes, on a just a handful of cells or their
contents. While the prediction may turn out to be overly
optimistic, there is no doubt that nanotechnology may well open
the way for a new generation of cancer treatments that are more
effective and less damaging than those currently available.
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