Leiden chemist fights cancer with chemotherapy and light
Leiden University chemist Sylvestre Bonnet is working on a method to fight cancer by combining new anticancer molecules and light irradiation of tumour cells. The new molecules are “phototoxic”: they do not work in the dark, but become very toxic once they are irradiated with light. This method may prevent side effects during chemotherapy. Bonnet has been awarded a European and a Dutch grant for this research, together worth more than 2.2 million euros.
Bonnet is keen to emphasise that he is doing fundamental research. He works with molecules and cells rather than patients. However, his research could have serious consequences for the development of photochemotherapy in the treatment of cancer. He was recently awarded a prestigious 1.4 million euro European ERC Starting Grant for this research; in 2012 he also received a Dutch Vidi grant of 800,000 euros. These votes of confidence will enable him to design new anti-cancer molecules that can be activated by light. The results may help reduce the side-effects of chemotherapy as well as contributing to developing photodynamic therapy, a patient-friendly cancer treatment.
Several anti-cancer medications such as cisplatin contain metal ions. The toxicity of the metal ion treats the cancer cells, but it also causes damage to healthy cells. This is because many metals are able to bind to biomolecules such as DNA. Bonnet intends to fight cancer with molecules containing another metal: ruthenium. Ruthenium can also bind to biomolecules, but it has photochemical properties as well, which means that light can cause the ruthenium complex to change.
Bonnet has come up with a way to switch on the toxicity of ruthenium prodrugs, making the molecule harmful only to cancer cells. In a recent publication in Chemistry – a European Journal he showed that biotin or methionine can be used to modify ruthenium complexes and prevent the ruthenium ion from binding to other biomolecules. Biotin or methionine form what is known as a ‘protective group’. By irradiating the ruthenium complex with visible light, the protective group is removed, and the ruthenium ion recovers its ability to bind to biomolecules, thus regaining its toxicity. Bonnet says, ‘The idea is to administer the protected compound, wait until it has penetrated the cancer cells, and then irradiate the cells with light in order to activate the new molecule locally and destroy the cancer cells. Any cell that is not irradiated (in the future this will be a patient’s body) is consequently spared.’
His grants will enable Bonnet to enlist seven researchers to build upon his work. ‘Our concept originated from purely fundamental research into what are known as “molecular machines”. Fundamental research can lead to unexpected applications; in this case, improving cancer treatment. We have patented our idea, but a university is not a pharmaceutical company. We will need to work with medical institutes and private partners if we want our new molecules to reach the patient.’
Apart from that, Bonnet adds, the focus is to ensure that as much as possible of the medication ends up in the tumour rather than elsewhere in the body. ‘That is what we, like many other reasearchers, are trying to achieve using nanotechnology. Only a fraction of the chemotherapy treatments that are currently available actually end up in the tumour. But with our new method this won’t lead to major problems for the patient. As long as our molecule is not activated by light it is much less harmful. It will thus leave healthy cells untouched until it is excreted by the body. As long as the medication is still in the body the patient will have to be protected against light, however.’
ERC & VIDI Grant for own research line
(28 January 2013)
Fundamentals-of-science is one of the six research themes at Leiden University
Health life and biosciences is one of the six research themes at Leiden University