X‐Ray‐triggered Carbon Monoxide and Manganese Dioxide Generation based on Scintillating Nanoparticles for Cascade Cancer Radiosensitization

Carbon monoxide (CO) is an endogenous signaling molecule with broad therapeutic effects. Here, a multifunctional X-ray-triggered carbon monoxide (CO) and manganese dioxide (MnO₂ ) generation nanoplatform based on metal carbonyl and scintillating nanoparticles (SCNPs) is reported. Attributed to the radioluminescent characteristic of SCNPs, UV-responsive Mn₂ (CO)₁₀ is not only indirectly activated to release CO by X-ray but can also be degraded into MnO₂ . A high dose of CO can be used as a glycolytic inhibitor for tumor suppression; it will also sensitize tumor cells to radiotherapy. Meanwhile MnO₂ , as the photolytic byproduct of Mn₂ (CO)₁₀ , has both glutathione (GSH) depletion and Fenton-like Mn²⁺ delivery properties to produce highly toxic hydroxyl radical (⋅OH) in tumors. Thus, this strategy can realize X-ray-activated CO release, GSH depletion, and ⋅OH generation for cascade cancer radiosensitization. Furthermore, X-ray-activated Mn²⁺ in vivo demonstrates an MRI contrast effect, making it a potential theranostic nanoplatform.