[article type: nannews]

[date: 13 January 2005]

[Title]

Can cadmium nanoparticles be safe?

[Teaser]

Assessing the dangers of nanoparticles is no simple matter.

[author]

Philip Ball

[Illustration: Copyright requested. This is the Top right image in Fig. 1 of the paper.]

[Caption]

Red and green fluorescent CdSe/ZnS nanoparticles (yellow where they coincide) inside breast-cancer cells stained so that the cell nuclei show up as blue. The big image is a composite fluorescence/optical microscope image; the inset shows fluorescence only. These particles are coated with an organic acid along with a silica shell bearing phosphonate groups.

[Standfirst]

Are cadium-containing fluorescent nanoparticles toxic to cells? That seems to depend sensitively on what the cadmium-based semiconductor is coated with.

[Text]

Fluorescent, semiconducting nanoparticles containing the toxic heavy-metal cadmium can be rendered biocompatible — relatively harmless to cells — by giving them a suitable surface coating, researchers in Germany have concluded1.

But they warn that it may not be a simple matter to make such nanoparticles ‘safe’. Wolfgang Parak of the Ludwig Maximilians University in Munich and co-workers say that the ‘leakage’ of cadmium ions from such particles isn’t the only way that they can damage or kill cells.

So they say that any study of the potential hazards of nanoparticles in biological research and biomedical applications will have to take careful note of exactly where the particles end up when in contact with living cells — whether, for example, they are ingested into the cells, stuck to the cell surface, or simply floating freely outside the cells.

The possible toxicity of nanoparticles is a pressing issue because of their proposed uses in medicine and cosmetic products, as well as the risk that humans and other organisms could become inadvertently exposed to nanoparticles released into the environment from other applications (such as information technology). This potential danger has been flagged as one of the key safety issues associated with the emergence of nanotechnology as an industrial and commercial venture2. But at present there is still relatively little known about such hazards.

Previous studies have suggested that water-borne carbon nanoparticles — colloidal aggregates of fullerene molecules — might have detrimental effects on fish3, but also that such effects could be ameliorated by changing the surface chemistry of the fullerene molecules4. The cytotoxicity of nanoparticles made from semiconducting cadmium selenide has also been investigated: for example, Sangeeta Bhatia and colleagues from the University of California at San Diego showed a year ago that these particles could be acutely toxic, but that their harmful influence could be reduced by coating the particles with a different material (zinc sulphide) to inhibit the migration of cadmium ions from the particle surfaces into solution5.

That sounded like good news. CdSe nanoparticles are fluorescent at visible wavelengths — the precise colour depends on the particle size, and so it can be conveniently tuned to make a range of ‘differently coloured’ nanoparticles from the same material. These tiny fluorescent clusters of atoms can be used to tag specific molecules, cells or tissues in biomedical research, and so they might be a tremendously useful tool — provided that they don’t turn out to be lethal to cells.

Parak and colleagues have now followed up the earlier studies with a closer look at just how toxic CsSe nanoparticles are, how they induce cell death, and how this might best be prevented. They have looked at the effects of a range of different particles, with various surface coatings, on a range of cell types.

A key question is whether such particles get inside cells in the first place. The researchers found that CdSe nanoparticles capped with a layer of ZnS (with total diameters of around 10–24 nm) are ingested into breast-cancer cells more or less regardless of their size or the nature of their surface coating. (Such particles are often coated with a surface layer of organic molecules such as organic acids or polymers.) Inside the cells they are held in vesicles surrounding the cell nucleus.

The only significant exception was for particles coated in a layer of silica combined with polyethylene glycol (PEG), for which uptake by the cells was rather low if the particles were small. So if you don’t want your particles to enter the cells, that’s how to do it.

Parak and colleagues verified the earlier finding5 that a shell of ZnS reduces the cytotoxicity considerably — by around tenfold — compared with ‘naked’ CdSe nanoparticles. They show that the important factor seems to be not simply the overall concentration of the nanoparticles in solution, but the concentration of cadmium atoms at the particle surfaces — smaller CdSe nanoparticles have a higher surface-to-volume ratio and so tend to be more toxic than an equivalent mass of larger particles. This supports the idea that cadmium release from the surface of the particles is the main cause of cell death in that case.

A silica-PEG coat seems to be a particularly good way to prevent escape of cadmium from the nanoparticle cores. This, combined with the fact that a silica-PEG coat reduces cell uptake of the particles, means that they were virtually non-toxic for the whole concentration range that the researchers studied (that is, Cd surface atom concentrations of up to 30 mM).

But cadmium is not the only potential hazard. Akiyoshi Hoshino at the International Medical Centre of Japan and co-workers have found previously that ZnS-capped CdSe particles can still be toxic, and that this seems to depend not on the cadmium content of the particles but on their surface chemistry and the way this affects their interaction with cells6. Parak and colleagues now find that nanoparticles coated with polymers seem to impair cells regardless of what the inorganic particles are made from: ‘inert’ gold nanoparticles are as troublesome as CdSe/ZnS. That appears to be the result of particles precipitating onto the cell surface and simply clogging them mechanically.

All of this might be seen as rather encouraging, however. Although there are no grounds for complacency about the hazards of nanoparticles containing toxic substances, it appears that careful engineering of the particles to ‘seal in’ the poisons and to determine exactly how the particles interact with cells might allow researchers to use these little beacons safely both in biological research and ultimately within the human body.

References

  1. Kirchner, C. et al. Cytotoxicity of colloidal CdSe and CdSe/ZnS nanoparticles. Nano Lett. advance online publication 31 December 2004.
  2. Nanoscience and Nanotechnologies: Opportunities and Uncertainties. Royal Society, 2004. See http://www.nanotec.org.uk/finalReport.htm.
  3. Oberdörster. E. Manufactured nanomaterials (fullerenes, C60) induce oxidative stress in the brain of juvenile largemouth bass. Environ. Health Perspect. 112, 1058-1062 (2004). [doi:10.1289/ehp.7021]
  4. Sayes, C. M. et al. The differential cytotoxicity of water-soluble fullerenes. Nano Lett. 4, 1881-1887 (2004). [doi:10.1021/nl0489586]

5.  Derfus, A. M., Chan, W. C. W. & Bhatia, S. N. Probing the cytotoxicity of semiconductor quantum dots. Nano Lett. 4, 11-18 (2004) [doi: 10.1021/nl0347334]3-2169

  1. Hoshino, A. et al. Physicochemical properties and cellular toxicity of nanocrystal quantum dots depend on their surface modification. Nano Lett. 4, 2163-2169 (2004) [doi:10.1021/nl048715d]