Universiteit Leiden

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Fighting tumours with light

Chemotherapy that does nothing until you irradiate it with light. Sylvestre Bonnet receives a Vici grant of 1.5 million euros for the development of this treatment. The Leiden chemist wants to build a new molecule to fight tumours that are at the time still difficult to treat.

Chemo with light

‘Ordinary chemotherapy makes too little distinction between good and bad cells', Bonnet explains. 'It kills not only cancer but also healthy cells.' Together with his group he, therefore, works on molecules that do not pose a danger to the body, because they only become active under the influence of visible light. During treatment, a patient takes these medicines and lets them spread throughout the body. Then, by illuminating just the tumour, the drug only becomes active there and only the bad cells are attacked. 'Our molecules are naturally toxic but are protected by a light-sensitive group. If you irradiate them, this group disappears and the molecule can react with the target: the cancer cells.'

Without oxygen

Light therapy against cancer already exists and is called photodynamic therapy. The problem with the current therapy, however, is that it works only with oxygen. 'These molecules use the energy of light to activate the oxygen in the irradiated cancer tissue,' Bonnet says. As a result, it becomes more reactive and then destroys the cancer cells.' However, some tumours are poorly perfused and therefore low in oxygen. In these so-called hypoxic tumours, regular phototherapy does not work. Other therapies, such as radiation and regular chemotherapy, are also less effective against these type of tumours. That is why Bonnet focuses on this group. 'We make molecules that under the influence of light split into two toxic parts, without the influence of oxygen. These molecules can therefore also attack tumours with little oxygen. For this purpose, Bonnet uses metal complexes with the metal ruthenium.

Cancer-specific

With his Vici grant Bonnet wants to solve a second problem. 'The current light therapy focuses on DNA. An active molecule binds to a DNA molecule and destroys it, causing the entire cell to break down. The problem, however, is that DNA is not cancer-specific, because it is in every cell. Furthermore, hypoxic cancer cells are often resistant to DNA attacking molecules. That is why we want to make molecules that are more selective, that work on a protein that is specific to cancer'. But that is quite difficult, according to Bonnet. Whereas it was still relatively easy to bind metal to DNA, binding to a protein is a lot more complicated. 'If you want to block a protein with a molecule, that molecule must fit very specifically in the protein. That is quite tricky, because you have to deal with many criteria: the charge of the molecule, the hydrophobicity, the shape... it all determines whether it fits or not.'

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