Unlocking the potential of ommatins as sustainable photosensitizers for photodynamic therapy

Donna Huber on July 17, 2026

Diagram showing photodynamic therapy: light activates photosensitizer molecules such as ommatins, producing ROS and cell death, with high phototoxicity and no dark toxicity. Molecular structures and process arrows shown.

Photodynamic therapy (PDT) has demonstrated efficacy in cancer treatment, with recent advancements concentrating on photosensitizers that generate high levels of reactive oxygen species (ROS) upon light irradiation while exhibiting minimal dark toxicity. In this study, we explored the photophysical properties of ommatins, specifically xanthommatin (Xa), decarboxylated xanthommatin (Dc-Xa), and protected uncyclized xanthommatin (Uc-Xa), and assessed their potential applications in anticancer PDT. Uc-Xa exhibited light-dependent activity against HepG2 cells, with an EC50 of 266 nM under blue light, while remaining inactive in the dark. High-content imaging of HepG2 cells treated with Uc-Xa and blue light showed ROS levels 2.2 times higher than in cells treated in the dark. Transcriptomic analysis of Uc-Xa-treated HepG2 cells under blue light revealed activation of genes associated with stress-responsive pathways, including the integrated stress response, p53 signaling, and p38 MAPK, which may contribute to oxidative stress-associated cellular injury and cell death.

Arif Hussain, Anthony A Ruberto, Harsh Bhatia, Steven P Maher, Yifan Quan, Lili Huang, André Barateiro, Gia-Bao Nguyen, David Budil, Hannah Sayre, Robert G Griffin, Dennis E Kyle, Prakash T Parvatkar, Roman Manetsch. Bioorg Med Chem Lett. 2026 Jul 17:130737. doi: 10.1016/j.bmcl.2026.130737.