A GSH‐Gated DNA Nanodevice for Tumor‐Specific Signal Amplification of microRNA and MR Imaging–Guided Theranostics

Abstract Developing tumor‐responsive diagnosis and therapy strategies for tumor theranostics is still a challenge owing to their high accuracy and specificity. Herein, an AND logic gated–DNA nanodevice, based on the fluorescence nucleic acid probe and polymer‐modified MnO 2 nanosheets, for glutathione (GSH)‐gated miRNA‐21 signal amplification and GSH‐activated magnetic resonance (MR) imaging–guided chemodynamic therapy (CDT) is reported. In the presence of overexpressed miRNA and GSH (tumor cells), the nanodevice can be in situ activated and release significantly amplified fluorescence signals and MR signals. Conversely, the fluorescence signal is quenched and MR signal remains at the background level with low miRNA and GSH (normal cells), efficiently reducing the false‐positive signals by more than 50%. Under the guide of miRNA profiling and MR imaging, the tumor‐responsive hydroxyl radical ( · OH) can effectively kill tumor cells. Furthermore, the nanodevice shows catalase‐like activity and glucose oxidase–like activity with the performance of O 2 production and glucose consumption. This is the first time to fabricate a tumor‐responsive theranostic DNA nanodevice with tumor‐specific signal amplification of microRNA and GSH‐activated MR imaging for CDT, potential hypoxia relief and starvation therapy, which provides a new insight for designing smart theranostic strategies.