Enhanced Cancer Radiosensitization via Energy Transfer from Eu-Doped GdF₃ Nanoparticles to Methylene Blue in X-ray Photodynamic Therapy

We synthesized europium-doped gadolinium fluoride (GdF₃:Eu) scintillating nanoparticles conjugated to methylene blue (MB) for singlet oxygen (¹O₂) generation in X-ray-induced photodynamic therapy (X-PDT). The impact of MB conjugation on GdF₃:Eu nanoparticles (GdF@B) was analyzed, including size, polydispersity, and surface charge. Time-resolved photoluminescence analysis demonstrated that binding of MB to the nanoparticle surface is essential for enabling efficient resonant energy transfer (ET) from the GdF₃:Eu core to the MB molecules. ET efficiencies ≥97% were obtained. ¹O₂ production exhibited energy- and dose-dependent behavior under varying radiation conditions. MTT assays demonstrated relative toxicity to LLC lung cancer mouse cells, while maintaining good tolerability in A549 human cancer cells. Clonogenic assays showed significant cytotoxicity in A549 cells only after X-ray exposure, confirming a reduced clonogenic survival. Survival fraction curves were analyzed using the linear-quadratic model, the sensitization enhancement factor, and the dose enhancement factor, highlighting the contributions of both the high atomic number of GdF₃:Eu cores and ¹O₂ generation. The findings indicate that GdF@B enables deep-tissue ROS generation, overcoming light penetration limitations in traditional PDT. Additionally, these nanoparticles show potential to enhance radiotherapy efficacy in both conventional fractionated protocols and advanced radiosurgery techniques, offering a promising cancer treatment nanoplatform.