NaCe0.7FX:Gd0.1,Tb0.2 nanoscintillator as a new sonosensitizer for potentiating cancer sonodynamic-immune therapy

Trends in sonodynamic therapy (SDT) have stimulated greater research efforts toward the development of novel sonosensitizers due to their crucial roles in increasing reactive oxygen species (ROS). Herein, a new scintillator, NaCe0.7FX:Gd0.1,Tb0.2, was explored as an ultrasmall inorganic sonosensitizer for glutathione (GSH) depletion-enhanced SDT of cancer. Specifically, fluorine vacancy-donated defective NaCe0.7FX:Gd0.1,Tb0.2 scintillating nanodots (ScNDs) were prepared via a high-temperature reaction method. PEGylated ScNDs, namely ScND-PEG, exhausted GSH at first, which further augmented the sonodynamic performance of ROS generation. In vitro studies demonstrated that US-irradiated ScND-PEG exerted significant cytotoxicity on CT26 tumor cells by triggering immunogenic cell death (ICD). In vivo studies revealed that ScND-PEG-mediated enhanced SDT substantially inhibited tumor development by activating cytotoxic T lymphocytes and secreting antitumor proinflammatory cytokines. With the assistance of immune checkpoint blockade (ICB), improved antitumor outcomes were further obtained with prolonged survival time. Notably, no significant acute or chronic toxicity occurred during our treatment schedule based on ScND-PEG. Overall, our findings paved the way for identifying a new kind of ScND-based inorganic sonosensitizer as a reserve, which might open up new opportunities for advancing sonodynamic-immune oncotherapy.