Gadolinium‐Manganese‐Based Nanoplatform Reverses Radiotherapy Resistant Factors for Radiotherapy Sensitization and Computed Tomography/Magnetic Resonance Dual‐Modal Imaging

Insufficient reactive oxygen species originating from hypoxia and high glutathione (GSH) in the tumor microenvironment (TME) is an important reason for radiotherapy (RT) resistance. Currently, radiosensitizers that remodel TME are widely investigated to enhance RT. However, developing an effective nano‐radiosensitization system that removes radiotherapy‐resistant factors from TME to boost RT effect while visualizing tumor imaging to aid therapy remains a challenge. Herein, MnO 2 nanosheets are grown on the surface of ultrasmall Eu‐doped NaGdF 4 (NaGdF 4 :Eu 3+ ) nanoparticles and modified by biocompatible DSPE‐PEG 2000 to prepare NaGdF 4 :Eu 3+ @MnO 2 @PEG nanoparticles (denoted as GMP NPs) as a radiosensitizer, which not only can reverse the TME by degrading H 2 O 2 to produce oxygen and consuming high GSH but also achieve computed tomography (CT)and magnetic resonance (MR) imaging. When GMP NPs synergize with X‐ray, a better antitumor effect is achieved in both HeLa cells and tumor‐bearing mice, compared with X‐ray alone. In addition, both paramagnetic Mn 2+ ionsproduced by decomposing MnO 2 in TME and NaGdF 4 :Eu 3+ nanoparticles enhance T 1 ‐weighted MR imaging. NaGdF 4 :Eu 3+ nanoparticles containing high atomic number of Gd/Eu effectively attenuate X‐ray to enhance CT imaging. The work provides new insights for developing an efficient RT sensitization platform integrating antitumor therapeutic effect as well as CT/MR dual‐modal imaging.