Harnessing X-ray-Induced NIR-II Afterglow through ROS-Mediated Molecular Activation for Tumor Radiotheranostics

Organic afterglow probes activated by X-rays hold considerable potential for deep-tissue imaging and cancer therapy. However, their applications are often limited by short-wavelength emission and the inefficient X-ray-induced generation of reactive oxygen species (ROS). To overcome these challenges, we developed a molecularly engineered small-molecule probe that integrates deep-tissue imaging through X-ray-triggered afterglow (AGL) in the second near-infrared (NIR-II) window. This system features a chemiexcitable phenoxy-adamantylidene donor linked to a rhodamine-based perchlorate acceptor via a vinyl bridge, forming a conjugated donor-π-acceptor (D-π-A) architecture. The extended π-conjugation and reduced excited-state energy of this framework enable efficient NIR-II emission (up to ∼1100 nm). Upon X-ray irradiation, the generated singlet oxygen (¹O₂) adds to the adamantylidene unit, and the resulting chemiexcitation transfers the released energy to the rhodamine perchlorate acceptor to produce an NIR-II afterglow. Meanwhile, the probe enables sustained singlet-oxygen production, synergistically enhancing tumor cell eradication while reducing the required radiation dose. This integrated molecular design establishes a unified platform for NIR-II afterglow-guided radiotheranostics, demonstrating the potential of rational molecular engineering to address the limitations of conventional X-ray-responsive agents and achieve spatiotemporally controlled cancer diagnosis and treatment.