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

Abstract

AbstractCarbon 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.