say the researchers. Their device, which is 15mm2
,
and weighs around 30mg, could be implanted in a single operation, after which it could be used multiple times. It is currently implanted using keyhole surgery, but in future the team hopes to reduce the size further and fit it into the barrel of a biopsy needle. ‘The advantage of our device is that it can be placed essentially anywhere in the body,’ he says. ‘Regions like the liver and brain – not normally considered for PDT intervention – could become viable targets for therapy.’ The device was implanted in
mice, close to a tumour with bladder cancers (PNAS, doi:
pnas.org/cgi/ doi/10.1073/pnas.1717552115). The mice were then injected with a photosensitiser that responded to violet and red light wavelengths. The devices were powered remotely, and the dual red and violet emissions activated the drug. ‘Since only the tumour was
illuminated using the device, there were no off-target effects,’ said the researchers. ‘The mice in the treatment group all responded to the treatment, showing significant tumour regression. A second dose of treatment resulted in close to complete tumour shrinkage.’ A long-term aim is to add
biosensors to the device. This would provide immediate and frequent feedback to therapy, allowing for a more customisable approach, tailored to the needs to the individual, while making the process minimally invasive.
Treating metastasis Metastasis is the process of cancer cells spreading to other parts of the body. Once it has happened, the condition becomes very hard to treat successfully. If the cells spread to the bone marrow, for instance, any conventional treatment may harm the stem cells that are stored there. With its greater selectivity, PDT could be an effective alternative. Researchers at the University of Cincinnati, US, are working on a method that not only tracks down the cancer cells once they have spread – but also uses an innovative way of activating the photosensitiser. ‘Metastatic breast cancer can be a devastating diagnosis with high rates
of relapse and death, and there are currently no effective therapies,’ says Nalinikanth Kotagiri, an assistant professor in the university’s college of pharmacy. Rather than using an external light
source – like a lamp – the team is looking to use ‘Cherenkov radiation’. This is the light – in the UV portion of the spectrum – that is emitted by beta-particles from radionuclides. ‘It’s been used for imaging, to detect radiation in the body – so why not use the light to excite a photosensitiser?’ he says. The approach is radically different
to ‘conventional’ PDT, which tends to use light in the visible spectrum, typically at the red end between 600 and 1000nm wavelength. This is because wavelengths shorter than 600nm are typically absorbed by the blood, while those above 1000nm usually get absorbed by water. This required a photosensitiser
that would respond to light at this shorter wavelength. Kotagiri has been using a nano-sized titanium substance called titanocene dichloride. This was originally developed in the 1990s as a less toxic alternative to cisplatin. It got as far as Phase 2 clinical trials, but has since found use in the plastics industry as a polymerisation agent. ‘If we can make it work, we can bring this molecule back for clinical trials as a photosensitiser,’ he says. ‘We found it works well with Cherenkov radiation.’ As a light source, the team is
using a commonly used radio-nuclide called fluorodeoxyglucose (FDG). ‘It acts as a liquid light source,’ says Kotagiri.
Another potential advantage of this method is that is can generate ‘singlet oxygen’ even under hypoxic conditions, such as in the core of a
Researchers from the National University of Singapore, including John Ho (left) and Zhang Yong, say their wirelessly powered device could allow PDT to treat a wider range of conditions, such as brain and liver cancer
tumour. This is because titanocene dichloride creates free radicals from water in the cells, rather than from ‘triplet oxygen’. ‘This means the method is oxygen-independent,’ he says.
In addition, UV light is very easily 1cm
attenuated, meaning that it will not escape beyond the interior of a cell. As long as both the FDG and titanocene dichloride are together, the effect will be highly localised, which will prevent side effects. ‘Lipid membranes will stop UV
Depth into the skin that visible light will penetrate, so won’t reach most tumours within the body. Optical fibres can be used to deliver light to certain body cavities – such as the lungs or stomach, for instance – but the procedure can be invasive
Only one PDT photosensitiser is currently approved for cancer treatment. The drug, Tookad, is a palladium complex used to treat prostate cancer
Scientists have developed a potential way of improving PDT by calculating exactly when to perform light irradiation. Adding a nanoparticle ‘tracker’ to the photosensitiser allows its progress to be tracked accurately through the body
light,’ he says. ‘If I want a precise treatment, I don’t want my radiation to be in the visible range – as it could penetrate nearby cells.’ The titanocene dichloride, which is modified with tumour-targeting ligands, is injected first. After a few hours, the FDG is injected. In a paper in 2018, Kotagiri says the team showed that it could treat multiple myeloma in bone marrow without harming nearby stem cells (Nature Communications, doi: 10.1038/s41467- 017-02758-9). ‘Toxicity is limited to the tumour cells,’ he says. Kotagiri says that tailoring other
US Food and Drug Administration- approved light-sensitive drugs as radionuclide activated therapies could expand the scope and range of the diseases these drugs currently treat. ‘If proven beneficial, it could be ready for a patient population in five to 10 years, since all the materials involved have already been used in humans,’ he says. Despite its promise, PDT is still in its infancy. However, the growth of personalised medicine – and the very real prospect of avoiding the worst side effects of cancer treatment – means that more techniques are likely to come to fruition in the near future.
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