At the Institute of Organic Chemistry of the ELKH Research Centre for Natural Sciences (TTK), researchers from the Chemical Biology Research Group identified water-soluble blocking groups that can be cleaved with green, orange, or red light in their latest research aimed at increasing the selectivity of chemotherapeutic agents. These blocking groups enable the clinical translation of photoactivatable chemotherapy. The paper presenting the results was published in one of the most prestigious chemical journals, the Journal of the American Chemical Society
Minimizing the unwanted side effects of therapeutic agents is one of the major challenges in drug research. Such challenges are addressed with targeted therapies, where the effect of the drug is restricted to the vicinity of malignant cells. Among the different targeted approaches, photochemotherapy is receiving ever more attention.
Photoactivated chemotherapy (PACT) combines the beneficial effects of external radiation therapy and internal chemotherapy and offers excellent localization precision in the case of localized primary tumors. PACT relies on the use of photolabile protecting groups (photocages) that transiently disable the biological activity of cytotoxic drugs (payload, cargo) through a specific covalent linkage. Light irradiation of such photoresponsive prodrugs triggers the release of the reactivated drug via bond cleavage (photo-uncaging).
Despite its advantages, clinical translation of PACT is still hindered by the lack of water-soluble, visible-light activatable photocages suitable for in vivo applications. In their latest paper, researchers from TTK report on the development of water-soluble, green-orange-red light-responsive photocages that greatly facilitate the translation of PACT to clinical applications.
Publication:
Alexandra Egyed, Krisztina Németh, Tibor Á. Molnár, Mihály Kállay, Péter Kele*, and Márton Bojtár* (2023). Turning Red without Feeling Embarrassed─Xanthenium-Based Photocages for Red-Light-Activated Phototherapeutics. Journal of the American Chemical Society. Doi: 10.1021/jacs.2c11499