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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 visible spectrum.

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.

Source

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.

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