ONOO– Activatable Fluorescent Sulfur Dioxide Donor for a More Accurate Assessment of Cell Ferroptosis

Ferroptosis is critical in the treatment of tumor therapies. Thus, monitoring reactive oxygen species (ROS) is of great significance for accurate assessment in ferroptosis without any interference. However, current probes for monitoring ROS during ferroptosis suffer from a drawback in that the probes consume ROS during detection, which inhibits the ferroptosis process and thus affects the accuracy and effectiveness of monitoring the process of ferroptosis. Herein, a new fluorescent donor probe, TFMU-SO₂D, with the combination of the moiety of the SO₂ donor is designed and synthesized by introducing the aryl boronate moieties that could give it the ability to effectively recognize ONOO^-. The released SO₂ could consume excess glutathione and regulate oxidative stress by elevating ROS levels, which would offset the ROS depletion by TFMU-SO₂D and ensure accuracy in monitoring the ferroptosis process. The experimental results demonstrated that TFMU-SO₂D possessed satisfactory performance for monitoring ONOO^- as well as simultaneously releasing SO₂ in oxidative stress stimulated by monensin and ferroptosis stimulated by erastin and RSL3. Additionally, the capability of SO₂ synergized with ferroptosis to inhibit the viability of cancer cells was demonstrated by the CCK8 assay, which may be due to the fact that SO₂ can potentiate ferroptosis cell death by increasing the ROS level. Overall, these combined results indicated that TFMU-SO₂D possesses the excellent ability to precisely monitor ONOO^- during ferroptosis without interference, which is significant for accurately accessing ferroptosis, cancer treatment, and drug development.