Abstract:

Background and purpose: Laryngeal cancer is a refractory malignant tumor in otolaryngology. Radiotherapy and chemotherapy combined with surgery are often used, however, this treatment method has little improvement on the 5-year survival rate and mortality of patients, and is often accompanied by loss of laryngeal function and drug resistance. This study aimed to explore the effect of sonodynamic therapy (SDT) mediated by nanoacoustic sensitizer T-G-C particles on inhibiting human laryngeal cancer cells, and to provide a new non-invasive treatment for laryngeal cancer. Methods: Based on the synthesized T-G-C nanomaterials, the uptake of nanomaterials by Tu686 cells was evaluated under confocal laser scanning microscope, and the cell survival and apoptosis were evaluated by cell counting kit-8 (CCK-8) and Annexin Ⅴ- fluorescein isothiocyanate (FITC) reagent in the presence of ultrasound. BALB/c nude mouse xenograft model was established. The weight and tumor changes of mice were recorded during the treatment by injecting different types of drugs and ultrasonic irradiation in the tumor area, and the treatment effects were analyzed and compared. The apoptosis and necrosis of tumor cells and the production of reactive oxygen species (ROS) were compared by H-E, TUNEL, Ki-67 and DHE stainings. Results: Nanomaterials and cells incubated for 24 hours had no obvious toxicity, only led to the decline of cell survival rate under ultrasonic stimulation, and the cells showed mainly early apoptosis and late apoptosis. In the animal experiment, only after intratumoral injection of drugs and ultrasound treatment on the 1st, 3rd, 5th and 7th days, the tumor growth of mice in T-G-C+ultrasound group was significantly inhibited, and the tumor inhibition rate is 100%. After 16 d of treatment, obvious red fluorescence could be seen in the tumor area after ultrasound irradiation, which demonstrated that the core of tumor inhibition was the production of ROS. Conclusion: Biocompatible T-G-C nanoparticles stimulate the synergy of SDT and piezoelectric therapy when stimulated by ultrasound, and promote the early and late apoptosis of laryngeal cancer cells through ROS, which provides a combined treatment method for laryngeal cancer and promotes the application of multidisciplinary therapy in department of otolaryngology.

Key words: Sonodynamic therapy, Laryngocarcinoma, Nanomaterials, Sonosensitizer, Reactive oxygen species