Plasmonic nanoparticles heat up upon NIR light exposure for cancer treatments

Researchers ar ETH Zurich in Switzerland have developed nanoparticles that heat up when they absorb near-infrared (NIR) light, enabling them to kill tumor tissue with heat. What's more, the nanoparticles are relatively easy to produce and have a wide range of applications.

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Gold is a popular material for nanoparticles used therapeutically, as it is well tolerated and does not usually trigger any undesirable reactions. In the characteristic ball or sphere shape of nanoparticles, however, gold does not have the necessary properties to work as a plasmonic particle that absorbs sufficiently in the NIR spectrum to heat up. To do so, it needs to be molded into a special shape, such as a rod or shell, so that the gold atoms adopt a configuration that starts absorbing NIR light, thereby generating heat. Producing such nanorods or nanoshells in sufficient amounts, however, is complex and expensive.

So the researchers, led by Sotiris Pratsinis, professor of particle technology at ETH Zurich, have discovered a trick to manufacture plasmonic gold particles in large amounts. They used their existing knowledge on plasmonic nanoparticles and made sphere-shaped gold nanoparticles that display NIR plasmonic properties by allowing them to be aggregated. Each particle is coated with a silicon dioxide layer beforehand, which acts as a placeholder between the individual spheres in the aggregate. Through the precisely defined distance between several gold particles, the researchers transform the particles into a configuration that absorbs NIR light and thus generates heat.

"The silicon dioxide shell has another advantage," explains Georgios Sotiriou, first author on the study and, until recently, a postdoc in Pratsinis' research group and currently an SNF Fellow at Harvard University (Cambridge, MA). "It prevents the particles from deforming when they heat up," he adds, which is a major problem with nanorods. If the rods lose their shape while heating up, they lose their desired plasmonic properties and are no longer able to absorb enough NIR light to generate heat.

The researchers have already tested the new particles on breast cancer cells in a Petri dish and discovered that after exposure to NIR light, the nanoparticles heated up sufficiently to kill off the cells while cells survived in control experiments (with particles, but without radiation, and with radiation, but without nanoparticles).

To be able to steer the particles specifically towards cancer tissue, the researchers also mixed superparamagnetic iron oxide particles in with the gold particles, which enable the nanoaggregates to be controlled via magnetic fields and may enhance their accumulation in a tumor. Moreover, this opens up the possibility of heating the aggregates in deep layers of tissue that IR light can no longer reach via magnetic hyperthermia. Here, the heating of the particles is induced by a magnetic field, where the plus and minus poles alternate at a rapid rate.

"A lot of questions still need to be answered before the particles can be used in humans," says Jean-Christophe Leroux, professor of drug formulation and delivery at ETH Zurich, who was also involved in the research project. Although gold, silicon dioxide, and iron oxide are well tolerated, what happens to the particle aggregates in the body in the course of time--whether they accumulate in the liver or are broken down and excreted, for instance--still needs to be investigated.

The hybrid iron oxide-gold nanoparticles are not only able to kill off tumor cells through heat; they could also be used as a contrast medium for imaging processes in diagnostics by magnetic resonance imaging, as investigated in collaboration with University Hospital Zurich, or as part of a vehicle that carries active substances. "You could even couple the particles with temperature-responsive drug carriers, which would then allow the drug release if a certain temperature were exceeded," explains Sotiriou. This would allow undesirable side effects on the rest of the body to be reduced or even avoided.

Full details of the work appear in the journal Advanced Functional Materials; for more information, please visit http://dx.doi.org/10.1002/adfm.201303416.

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