A Dual GSH/ROS-Functional NIR Fluorescent Platform for Synergistic Photodynamic Therapy and Radiosensitization in...

High-precision tumor theranostic systems capable of real time monitoring are imperatively required for optimizing the spatial targeting accuracy during radiotherapy and surgical resection across clinical management of nasopharyngeal carcinoma (NPC). However, the clinical application of photodynamic therapy (PDT) is impeded by the suboptimal reactive oxygen species (ROS) generation efficiency and inadequate visualization of redox procedure. In this study, we developed a theranostic platform HSF, featuring integrated tumor-specific near-infrared (NIR) fluorescence imaging and photodynamic ROS generation for real time monitoring and targeted radiotherapy of solid malignancies for NPC. Mechanistically, HSF was initially activated by the elevated glutathione (GSH) levels in the tumor microenvironment, which concomitantly turned on its NIR fluorescence and photodynamic properties. The resulting NIR fluorescence allowed for tumor visualization, while the PDT-triggered oxidative stress further consumed intracellular GSH, thereby ultimately inducing ferroptosis. In NPC cell-derived xenograft models, HSF demonstrated exceptional biocompatibility and effective in vivo retention. This multifunctional photosensitizer enabled precise radiotherapy navigation via real time fluorescent monitoring and ferroptosis-mediated therapeutic mechanisms, offering a transformative approach for real time visualization-guided NPC therapy.