Most conventional optical imaging techniques are not suitable for imaging thick living tissue because light is strongly scattered by biological matter, which leads to poor spatial resolution. Photoacoustic imaging does not suffer from this problem because it measures the thermoelastic expansion (or heat) produced by the absorption of photons. The technique works because photons sent into a sample in pulses (for example, using a femtosecond laser), heat up the water in surrounding tissue, causing it to expand and contract with each pulse. The pressure waves produced as a result propagate out from the expanding structures and these can be detected by an ultrasound transducer.

Efficient though it is, the technique still requires contrast agents because although some biological molecules – such as haemoglobin and melanin – show natural photoacoustic contrast, most do not. Although a number of such agents, including small-molecule dyes, metallic nanoparticles, carbon nanotubes and porphysomes, have been developed, most do not produce a strong enough photoacoustic signal or are not very stable when exposed to high energy laser beams.

Better on a per mass basis

Now, a team led by Jianghong Rao, Zhenan Bao and Sam Gambhir has shown that semiconducting pi-conjugated polymers are excellent contrast agents for photoacoustic molecular imaging in vivo – and are better on a per mass basis at producing a signal in mice than the best known photoacoustic contrast agents, carbon nanotubes and gold nanorods. The two polymers studied are called poly(cyclopentadithiophene-alt-benzothiadiazole) and poly(acenaphthothienopyrazine-alt-benzodithiophene).“What is more, the signal from these polymer nanoparticles also appears to be enhanced by specific chemical mediators such as reactive oxygen species, which are involved in the onset and progression of many pathologies,” explains Rao.

“Such semiconducting polymers are traditionally used as the light-emitting layer in organic light-emitting diodes (OLEDs) to convert electricity into light, or as the active layer in solar cells to convert sunlight into electricity,” he told “We have now shown that the polymers formulated into water-soluble nanoparticles can absorb a large amount of near-infrared light. The absorbed energy is then dissipated as heat to generate sound waves and these waves can be exploited for photoacoustic imaging.”

More biocompatible

And that is not all: since the semiconducting polymers are organic, they are more biocompatible than other commonly used contrast agents such as metallic nanoparticles and semiconducting quantum dots, he added. “They are also more resistant to oxidation and last longer under laser light irradiation than these inorganic nanoparticles, making them better as contrast agents for long-term medical imaging applications.”

The Stanford team says that it is now looking at applying its technique to cancer imaging by adding specific tumour recognition groups onto the nanoparticles’ surfaces. Such modifications would not affect the spectral properties of the nanostructures but would make them better at seeking out specific types of cancer cell. “We will also be looking at polymers that absorb at different near-infrared wavelengths so that we can simultaneously carry out multiple target imaging,” said Rao. “There is much to study in these semiconducting nanoparticles, from basic science to biomedical applications.”

The present work is detailed in Nature Nanotechnology doi:10.1038/nnano.2013.302.

Further reading

CNTs as contrast agents in photoacoustic imaging (Oct 2008)
Nanocages could help treat tumours (Dec 2011)
Golden nanotubes show super contrast (Sep 2009)
Antibody-guided carbon nanotubes target cancer (Mar 2009)
CNT nano-springs make skin-like sensor (Oct 2011)