Pure organic phosphorescent scintillator for glucose metabolism regulation-enhanced low-dose X-ray-induced photodynamic therapy

X-ray-induced photodynamic therapy (X-PDT) leverages the penetration power of X-rays to generate reactive oxygen species (ROS) within deep tissues for cancer treatment, merging the benefits of both photodynamic therapy and radiotherapy. Traditional X-PDT, however, typically relies on inorganic scintillators containing heavy-metals to act as energy transducers, exciting nearby photosensitizers to produce singlet oxygen. Moreover, the hypoxia conditions prevalent in tumors can severely diminish the efficacy of X-PDT. Here, we report a metal-free, self-enhanced organic phosphorescent nanoscintillator (termed OPSG NPs) capable of efficiently generating singlet oxygen under low-dose X-ray irradiation, facilitated by glucose metabolism regulation. OPSG NPs are constructed through a self-assembly behavior driven by molecular interactions between an organic phosphorescent scintillator and a glucose transporter 1 (GLUT1) inhibitor. The OPSG NPs serve dual functions, acting as both scintillator and photosensitizer, which can be activated by direct X-ray irradiation. Additionally, they possess the ability to inhibit glucose supply and reduce oxygen consumption for tumor cell respiration. This strategy effectively alleviates the hypoxia within the tumor microenvironment and consequently enhances the therapeutic efficacy of X-PDT. Both in vitro and in vivo studies demonstrate the excellent antitumor X-PDT performance. This glucose metabolism regulation-enhanced low-dose X-PDT strategy paves the way for more efficient therapy against deep-seated tumors.