Structurally Engineered Organic Photosensitizer Enabling Synergistic Photodynamic and Photoacid Therapy via ROS and...

The development of multiactive photosensitizers integrating the functions of photodynamic therapy (PDT) and photoacid therapy (PAT) provides a new strategy for overcoming tumor drug resistance and enhancing therapeutic efficacy. In this study, we designed and synthesized an organic photosensitizer, CzC, with a twisted molecular structure consisting of carbazole and thiophene linked by covalent bonds. This molecular design endowed CzC with excellent light absorption, good photostability and efficient ROS and H⁺ release under 365-nm laser irradiation. This bifunctional response mechanism synergistically disrupts intracellular acid-base homeostasis and triggers oxidative stress to promote tumor cell apoptosis. In vitro, CzC showed good cellular uptake, potent ROS/H⁺ generation, and very low dark toxicity; in vivo in a mouse 4T-1 tumor model, CzC significantly inhibited tumor growth under light activation, and no systemic toxicity or organ damage was observed. This study demonstrates that CzC is an organic photosensitizer with structural designability, photostability, and bimodal therapeutic function, and provides a powerful candidate molecule for next-generation phototherapy.