Tiny nanospindles enhance use of ultrasound to fight cancer

8 Dec 2020
Tiny nanospindles enhance use of ultrasound to fight cancer

Ultrasound can be used to treat cancer when used in combination with molecules that sensitise the system to sound waves.

These sonosensitisers generate toxic reactive oxygen species that attack and kill tumour cells.

In Applied Physics Reviews, by AIP Publishing, scientists from Soochow University in China report a new type of sonosensitiser based on a vanadium-doped titanium dioxide, V-TiO2, that enhances the amount of damage ultrasound inflicts on tumors. Studies in mice showed that tumor growth was markedly suppressed when compared to a control group.

Organic molecules have been used in the past as sensitisers, but these are unstable and can lead to phototoxicity, where exposure to light can produce rashes or extreme sunburn.

Inorganic sensitisers based on TiO2 nanomaterials are also used, but these do not work well and can remain in the body for long periods.

TiO2 does not work well as a sensitiser, because it has a wide band gap in its electronic structure.

Even when the ultrasound strips electrons away from the TiO2 nanoparticles, the electrons rapidly recombine with the nanoparticles, preventing the generation of reactive oxygen species that could attack tumour cells.

The investigators realised they could avoid this effect by doping TiO2 nanoparticles with the metal vanadium to form nano-sized spindles.

"The band gap of V-TiO2 nanospindles is reduced, increasing the efficiency of ultrasound-triggered reactive oxygen species production compared to that of pure TiO2 nanoparticles," said author Liang Cheng.

The microenvironment around the tumour is key to cancer metastasising and invading other tissue, and important for the way chemotherapy and other treatments work.

The tumour microenvironment has an acidic pH but also contains a lot of hydrogen peroxide and a substance known as glutathione.

The investigators realised the V-TiO2 spindles act like tiny enzymes that catalyse chemical processes in the microenvironment.

In the presence of ultrasound waves, the spindles allow a two-pronged attack on the tumour: one involving sound waves, the other a type of chemotherapy that degrades hydrogen peroxide and consumes glutathione.

Both effects kill tumour cells without harming healthy tissue.

The investigators carried out a careful study using controls on both breast cancer tumour cells and on mice infected with these cancerous cells.

In addition to direct measurements about tumour growth, they employed fluorescent probes to visualise reactive oxygen species and glutathione during the process.

"It is worth noting that V-TiO2 nanospindles are rapidly excreted from the body," said Cheng. "This helps prevent any possible long-term toxicity effects."

The scientists were also able to observe V-TiO2 nanospindles in the spleen and liver of the mice and, later, in the faeces and urine.

No obvious signs of organ inflammation or damage were observed, showing that these sensitisers are both safe and effective.