ISIS Report 20/11/03
Metal Nanoshells, Cure or Curse?
Among the nanoparticles developed for use in medical and other
applications are non-biodegradable metal nanoshells. Has enthusiasm to exploit
their remarkable properties run too far ahead of safety considerations ?
Dr. Mae-Wan Ho reports.
Metal nanoshells are a class of nanoparticles with tunable resonance to
electromagnetic radiation. They consist of a spherical dielectric core
nanoparticle, such as silica, surrounded by a thin metal shell, such as gold.
These particles possess a highly tunable plasmon resonance,
whereby light of particular frequencies causes collective oscillations of
conductive metal electrons at the nanoshell surface, thus greatly concentrating
the intensity of the light. Whereas many bulk metals demonstrate plasmon
resonance behaviour, they do so generally over a very small region of the
In nanoshells, however, their plasmon resonance can readily be tuned to
a wide range of specific frequencies, from the near ultra violet to the
mid-infra-red, simply by controlling the relative thickness of the core and
shell layers of the nanoparticle. This range spans the near infrared, a region
where absorption in tissue is minimal and penetration is optimal.
To date, nanoshells have demonstrated their usefulness in many
applications ranging from inhibition of photo-oxidation in photoluminescent
polymer films to biosensing and light-triggered drug delivery.
One possible application is in removing diseased tissues without
complicated surgery. Recently, lasers, microwaves, radiofrequency radiation,
and focussed ultrasound, have all been used to heat up and kill diseased
tissues selectively without invasive surgical procedures. But these can still
cause damage to intervening tissues.
Researchers in Rice University Texas USA thought that by tuning
nanoshells to strongly absorb light in the near infrared, where optical
transmission through tissue is optimal, nanoshells embedded in tissues can be
used to deliver a therapeutic dose of heat to the tissues by moderately low
levels of light applied outside the body.
In a paper just published in the PNAS (house journal of the US
National Academy of Sciences), the research team reported that human breast
carcinoma cells in culture incubated with nanoshells died when exposed to near
infrared light (820nm, 35W/cm2) while control cells not containing
nanoshells appeared unharmed.
Similarly, in live animals with solid tumours into which metal
nanoshells were injected, exposure to near infrared light (820nm, 4W/cm2)
caused the tumours to heat up by some 40C, while controls without nanoshells
heated up by less than 10C. Cells in tissues heated above the thermal-damage
threshold were killed, while control tissues appeared undamaged.
The gold surface of the nanoshell can also catalyse the self-assembly of
polyethylene glycol, antibodies, or a variety of other agents. This offers the
potential to target the nanoshells to specific diseased tissues.
But are the nanoshells safe? They are non-biodegradable and have
enhanced catalytic capabilities. What happens to the nanoshells in the dead
cells when they are cleared by the immune system? What effects do they have on
the health of the patient in the long term? What are the wider environmental
impacts when these nanoshells are discharged or released? None of these
questions have been addressed.
It is clear that enthusiasm to exploit the remarkable properties of
metal nanoshells and other nanoparticles have run far ahead of any safety
concerns. It is time for responsible scientists to impose a moratorium on
research and development until proper safeguards are put in place.
Hirch LR, Stafford RJ, Bankson JA, Sershen SR, Rivera B, Price RE, Hazle
JD, Halas NJ and West JL. Nanoshell-mediated near-infrared thermal therapy of
tumors under magnetic resonance guidance. PNAS 2003, 100, 13549-54.