Dual Pathways of Photorelease Carbon Monoxide via Photosensitization for Tumor Treatment

Carbon monoxide (CO) gas therapy, as an emerging therapeutic strategy, is promising in tumor treatment. However, the development of a red or near-infrared light-driven efficient CO release strategy is still challenging due to the limited physicochemical characteristics of the photoactivated carbon monoxide-releasing molecules (photoCORMs). Here, we discovered a novel photorelease CO mechanism that involved dual pathways of CO release via photosensitization. Specifically, the photosensitizer Chlorin e6 (Ce6) sensitized oxygen to produce singlet oxygen (1O2) and oxidized photoCORM Mn2(CO)10 to release CO in an air-saturated solvent under red light (655 nm, 50 mW/cm2) irradiation. Furthermore, Ce6 and Mn2(CO)10 could undergo multistep photochemical reactions to release CO, as well as the degradation of the photosensitizer Ce6 in an oxygen-depleted solution. As a proof of concept, we demonstrated the feasibility and tumor inhibition of this CO release strategy both in vitro and in vivo. These results provide a robust platform for the development of new approaches to CO-mediated modulation of signaling pathways and further facilitate the practical use of gas therapeutic methods in tumor therapy in vivo.