Novel YOF-Based Theranostic Agents with a Cascade Effect for NIR-II Fluorescence Imaging and Synergistic Starvation/Photodynamic Therapy of Orthotopic Gliomas

Accurate diagnosis and highly effective treatment of glioblastoma are still challenges in clinic. Near-infrared (NIR) light triggered fluorescence imaging and photodynamic therapy (PDT) showed the potential for theranostics of glioblastoma, but the presence of blood-brain barrier (BBB) and hypoxia limited treatment effect. Herein, the novel theranostic nanoagents with YOF:Nd³⁺ as core, MnO₂ as shell, and further loading photosensitizer (indocyanine green, ICG) and glucose oxidase (GOx) were successfully constructed, and further modified with lactoferrin to endow them with BBB penetration and target abilities (YOF:Nd³⁺@MnO₂-ICG-GOx-LF, YMIGL). The YOF:Nd³⁺ core with good fluorescence performances makes YMIGL act as promising probes for fluorescence imaging in the second biowindow (NIR-II FL). The combination of GOx and MnO₂ shell significantly increased the O₂ generation from the cascade reactions and consumed glucose, improving the treatment effect of PDT and achieving starvation treatment (ST). These theranostic nanoagents exhibit a highly efficient inhibition effect on orthotopic gliomas by cascade reactions, which improved PDT and ST.