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 <i>in vitro</i> and <i>in vivo</i>. 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 <i>in vivo</i>.