Ten years ERC: Sylvestre Bonnet kills cancer with light
In 2013, Sylvestre Bonnet received an ERC Starting Grant to kill cancer with molecules that can be activated by light. Two postdocs and three PhD students later, the end approaches of his so far successful project.
A benefit to science and society
I am very grateful to the ERC for this grant,’ says chemist Bonnet. ‘The two postdocs I could hire with the grant were really essential for this project. I needed their biological expertise to start the project and to train my PhD students in testing new compounds in cancer cells.’ Besides his research group, society also directly benefited from his grant, Bonnet explains. ‘Straight after receiving the grant, we purchased scientific instruments at private companies active in The Netherlands. In addition, the postdocs and PhD students of this project learned to think creatively, and they passed their insights to younger students. Many will take this creativity along to the industry,’ says Bonnet about the societal impact of ERC grants for fundamental research.
In his research, Bonnet uses metal complexes: molecules that consist of a positively charged metal ion and one or more electron-rich organic molecules. In this case, the metal is ruthenium. Metal compounds can be very toxic, but Bonnet neutralises the toxicity of the metal with a special kind of molecule: a light-sensitive protective group. ‘This group leaves the metal-containing molecule upon blue, green, or red light irradiation, thereby making the molecule toxic again,’ Bonnet explains. ‘By only illuminating the tumour, the harmful effects of the metal complex are limited to the tumour. Potentially, chemotherapy and radiotherapy combined, but without the side effects.’
Red or blue?
‘We have found different ruthenium metal complexes that can be activated by light, ’ says Bonnet. However, many of them require blue light for activation, which is not optimal for phototherapy. Not all colours are able to penetrate the body. ‘Red and near-infrared light are the best in penetrating the skin and body. However, their downside is that they lack the amount of energy necessary to activate most ruthenium-based compounds,’ Bonnet explains the problem. Fortunately, Bonnet proposed a solution that his PhD students proved right: ‘We can prepare drug-delivery systems that can upgrade red light into blue light in the body, which has enough energy to activate the metal compound,’ Bonnet says.
Motivated into the future
What Bonnet will do after this project ends? ‘I will continue with photopharmacology, because I think this research field is interesting for combining many disciplines, such as synthetic chemistry, photochemistry and cell biology.’ But he believes that another approach is vital in upcoming projects. ‘The metal complexes we have made destroy cells by binding to DNA. But clinically approved metal-based chemotherapy already works in a similar fashion. After chemo, the cells that remain are resistant to DNA-binding treatments. If we want our approach to be complementary to current treatments, our metal complexes should have a non-DNA target in the tumour.’ Bonnet is highly motivated to continuing this research: ‘I have been working on several grant applications. It is highly competitive, but the results we have gathered will help us to go forward!’
Publicaties tijdens ERC-beurs
- Influence of the Steric Bulk and Solvent on the Photoreactivity of Ruthenium Polypyridyl Complexes Coordinated to l-Proline
- Chemical Swarming: Depending on Concentration, an Amphiphilic Ruthenium Polypyridyl Complex Induces Cell Death via Two Different Mechanisms
- An in vitro cell irradiation protocol for testing photopharmaceuticals and the effect of blue, green, and red light on human cancer cell lines
- Green light-induced apoptosis in cancer cells by a tetrapyridyl ruthenium prodrug offering two trans coordination sites
Ten years of ERC
Sylvestre Bonnet conducts his research on killing cancer with light using a Starting Grant from the European Research Council (ERC). This year marks ERC’s anniversary. Over the course of the last ten years, roughly 70 researchers and/or research groups at Leiden University have been awarded ERC grants. As we approach the celebration of ERC’s anniversary on 23 June, we will be highlighting a number of our ERC research projects.