Researchers at IBEC and IDIBELL have developed a light-regulated molecule that could improve chemotherapy treatments by controlling the activity of anticancer agents.
Chemotherapy – the use of cytotoxic agents to kill the rapidly proliferating cells in tumors – is one of our main tools in the fight against cancer. However, its effectiveness and the body’s tolerance of it is often dramatically limited: it can affect healthy areas rather than just the cancerous ones, which causes side effects.
One way to deal with this would be to design ways to ensure that the drugs that are administered in chemotherapy are only activated when they’re at their desired target. Researchers in IBEC’s Nanoprobes and Nanoswitches group, who are pioneers in using light to remotely switch on or off the activity of drugs and other molecules, have now revealed such a possibility in the journal JACS.
In the study the researchers present phototrexate, a molecule that can be switched on and off remotely using light, that acts as an inhibitor of the dihydrofolate reductase (DHFR), an ubiquitous enzyme that plays an central role in the regulation of cell proliferation and growth. Phototrexate could therefore be used as a light-controlled variant of methotrexate, a widely prescribed chemotherapeutic drug used to treat cancer and psoriasis.
They tested phototrexate in zebrafish – a model organism that’s useful because of its similar genetic structure to humans – and showed that it strongly blocks DHFR in its photoactivated configuration, but is nearly inactive in its dark or ‘relaxed’ form.
“Phototrexate constitutes a proof-of-concept in designing light-regulated cytotoxic molecules,” says Carlo Matera, a researcher in IBEC’s Nanoprobes and Nanoswitches group and first author of the paper. “Our findings represent an important step towards the development of targeted anti-cancer photochemotherapies with localized efficacy and reduced side effects.”
Carlo Matera, Alexandre M. J. Gomila, Núria Camarero, Michela Libergoli, Concepció Soler, and Pau Gorostiza (2018). Photoswitchable Antimetabolite for Targeted Photoactivated Chemotherapy. JACS, just accepted manuscript