Precision Chemotherapy with a Photoswitchable Drug

Chemotherapy is one of the most common treatments for cancer. However, its therapeutic potential is in many cases seriously unsatisfactory due to the nonspecific drug distribution and off-target effects. Innovative chemotherapeutic treatments based on nanomedicine can increase therapeutic efficiency while reducing side effects to normal tissues. One emerging approach is photopharmacology, which relies on light-controlled nanoscale changes in the structure of a drug to turn its pharmacological activity “on” and “off” on demand. We have designed and developed the first photoswitchable inhibitor of the human dihydrofolate reductase and named it Phototrexate. Preliminary studies in vitro and in zebrafish demonstrated that Phototrexate behaves as a potent antifolate after illumination with UVA light and that it is nearly inactive in its dark-relaxed form. Moreover, early safety screenings revealed that it can be considered reasonably safe for further studies in animal models of disease. Overall, Phototrexate is emerging as a new drug candidate towards the development of high precision photochemotherapy.