Photothermal therapy is an up-and-coming tumour ablation technique that is less invasive than chemotherapy or surgery. Here, optical radiation is absorbed by noble-metal nanoparticles and transformed into heat. This heat is then used to thermally denature proteins and DNA in cells, and coagulate tissue. This irreversibly damages the targeted diseased cells, while minimizing damage to surrounding healthy tissue.

Gold nanoparticles are particularly interesting as anticancer agents in this respect because they are non-toxic and biocompatible. In particular, gold nanoparticles less than 2 nm in diameter (also known as gold quantum dots) can absorb light in the so-called near-infrared biological window (of between 650 – 900 nm), and convert it into photons and heat. Light of this wavelength can penetrate deeply into soft biological tissue, so allowing deep-lying tumours containing the nanoparticles to be reached and treated.

In addition to these distinct optical properties, gold quantum dots also have certain magnetic properties that are not seen in bulk gold or even gold nanoparticles larger than 2 nm. However, such small particles are often unstable in aqueous solution, such as that found in biological cells.

Quantum rattle is stable and non-toxic

Now, Molly Stevens and Matthew Hembury of Imperial College London together with co-workers at University College London, Louisiana State University in the US and the Laboratoire Chimie de la Matière Condensée in Paris, say that they have succeeded in placing gold quantum dots inside a mesoporous silica shell alongside larger gold nanoparticles within the shell’s central cavity. This structure, which looks rather like a baby’s rattle in miniature, is stable in aqueous solution, is not toxic to biological cells and the gold quantum dots inside it retain their photonic and magnetic properties.

In its experiments, the London–Paris–Louisiana team found that the new gold nanorattles can reduce the size of a tumour in a mouse by as much as 55% in just a single course of photothermal therapy.

Three ways of imaging

The photothermal effect can also be exploited to image a tumour in a technique known as photoacoustic imaging. When the gold quantum dots heat up, they temporarily dilate, a phenomenon that produces ultrasound waves that can then be detected during echography. A second way to image a tumour using the nanorattles comes thanks to the fluorescence emitted by the gold nanostructures when they are excited by near-infrared light. This fluorescence passes through biological tissue without being absorbed and can thus be measured to build up an image of the tumour. Finally, since the gold quantum dots are magnetic, they can be used as contrast agents in magnetic resonance imaging (MRI).

And that is not all: incorporating hydrophobic gold nanoparticles, inside a silica sphere allows the structures to carry significantly greater amounts of doxorubicin – a well-known anti-cancer drug. "Such anti-cancer agents are often difficult to stabilise in porous matrices but we have found that the amount of doxorubicin in the quantum rattles is nearly twice that in other more conventional vectors (such as liposomes)," Hembury tells

Sunjie Ye of the School of Physics and Astronomy and the Leeds Institute for Biomedical and Clinical Sciences at the University of Leeds in the UK, who was not involved in this research, says that the new work "brings applications of gold quantum dots to a new level, enabling this nanoplatform to be used as an 'all-in-one, see and treat' strategy against cancer. The smart synergistic design also offers a conceptually novel route for constructing multifunctional nanosystems."

Stevens and colleagues say that they are now busy trying to optimize their nanorattles and would like to functionalize the nanostructures' surfaces with biomarkers so that they can recognise specific target molecules – in particular different types of cancer cells. The researchers also hope to further reduce the size of the gold particles inside the central cavity so that the rattles are completely biodegradable.

The present work is detailed in PNAS doi: 10.1073/pnas.1419622112.