HEALTH AND WELL-BEING
– we can deliver it selectively into the nucleus of the cancer cell,’ she says. ‘This is something we didn’t expect.’ With the iridium photosensitiser
deposited into the cancer cell nucleus, light therapy would then be highly effective in targeting only those cells. There is plenty of research into attaching drugs to albumin in order to direct them to specific parts of the body. However, the Warwick team says it is not aware that any others have delivered drugs directly to the cell nucleus using this method. Part of the reason they achieved it is that the iridium drug is highly phosphorescent, which helped the researchers to track its progress in real time, using a microscope. While the team has proved the
photosensitiser’s final destination, however, it is still working to understand the mechanism behind it. While the albumin helps to deliver the iridium, it does not itself enter the nucleus. The testing was done in vitro, using cancer cells in culture. This included the use of 3D multicellular ‘spheroids’, which are a more realistic, three-dimensional representation of real cells. In vivo work would need to involve ‘suitable partners’, says Imberti. The Warwick
researchers have also been studying platinum compounds, for use when the usual mechanism of creating singlet oxygen is not available. This is often seen in the core of cancerous tissue, where there is a lack of oxygen – so-called hypoxic conditions. ‘Here, PDT does not work so well, so we use a light- activated molecule that decomposes to release toxic compounds,’ says Imberti.
Perfect timing Meanwhile, scientists in Russia have developed a potential way of improving PDT by calculating exactly when to perform light irradiation. When a photosensitiser is
injected into the body, it will take time to accumulate in a particular organ. Once it has accumulated, factors such as tumour size and the patient’s own metabolism dictate the
Below: The purple stain for cancer cell nuclei overlaps perfectly with the emission of green light from the iridium- albumin conjugate, showing the protein has delivered the photosensitiser to the nucleus of cancer cells.
Bottom: Iridium with its organic coat which is hooked up to the protein albumin (HSA). Together they enter cancer cells and deliver the iridium photosensitiser to the nucleus. On irradiation with blue light, the iridium not only glows green, but converts oxygen in the cell to a toxic form called triplet oxygen, which kills the cell.
most effective ‘window’ in which to perform irradiation – in order to have the maximum effect. Researchers from three institutes, including the National University of Science and Technology (Misis), have added a nanoparticle ‘tracker’ to the photosensitiser. This allows the photosensitiser’s progress through the body to be tracked accurately. ‘For maximum efficiency you must choose the time when accumulation is at its highest, and then irradiate,’ says Maxim Abakumov, head of the biomedical nanomaterials laboratory at Misis. ‘Timing is very important for photosensitisers.’ The technique works by tracking the magnetic particle using MRI, to which the photosensitiser is invisible. One challenge was to ensure that the two particles remained together in the body. ‘We’ve spent a year and a half on this, and are confident that they transport and work together,’ says Abakumov. Another challenge was to hook
the two molecules together. Because the photosensitiser is highly insoluble in water, the team needed to find a way to load it onto the magnetic particle. Abakumov adds that the optimal time of exposure to light can be anything from 30 minutes to four hours. Using MRI to track accumulation means there is no restriction on a tumour’s location. ‘You can track the tumour wherever it is,’ he says. ‘Depth does not matter.’ The concept has
been tested on three groups of mice for 21 days
By selecting where we shine the light, we reduce side effects
Cinzia Imberti Warwick University
(Pharmaceutics,
doi.org/10.3390/ pharmaceutics10040284). The groups were irradiated at three different times: 30 minutes after drug injection; between 60 and 100 minutes after injection; and after three hours. Almost all the mice in the second group showed a reduction in tumour growth, proving that irradiation timing was important. Abakumov stresses that this was a scientific study. While the team hopes to proceed to clinical trials, he says this is not like to happen for another three to five years. The technique offers further
potential to make PDT a personalised medicine technique. ‘We think our system will help identify the most appropriate irradiation time for each specific patient,’ he says.
Shining a light Because many parts of the body are impenetrable to light, PDT might be thought to be ineffective in these cases. However, researchers are developing increasingly ‘mobile’ forms of light that can irradiate the darkest recesses of the body. At the National University of
Singapore, for instance, researchers have developed a miniature implantable irradiation device, which can be charged wirelessly, and so requires no batteries. ‘Using this system, PDT, which was
limited to treating surface tumours, can now be applied to solid tumours in any part of the body,’ says Zhang Yong, one of the lead researchers on the project. Visible light will penetrate around
1cm into the skin, so cannot 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,
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