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

Abstract

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, MnO₂ nanosheets are grown on the surface of ultrasmall Eu-doped NaGdF₄ (NaGdF₄:Eu³⁺) nanoparticles and modified by biocompatible DSPE-PEG₂₀₀₀ to prepare NaGdF₄:Eu³⁺@MnO₂@PEG nanoparticles (denoted as GMP NPs) as a radiosensitizer, which not only can reverse the TME by degrading H₂O₂ 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 Mn²⁺ ionsproduced by decomposing MnO₂ in TME and NaGdF₄:Eu³⁺ nanoparticles enhance T₁-weighted MR imaging. NaGdF₄:Eu³⁺ 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.