Synergistic cytotoxicity effect of ultrasound and plasma microbubble in glioblastoma 3D tumor sphere model

The combined application of ultrasound (US) and plasma microbubble (PMB) is a promising technology against glioblastoma (GBM). Here, we determined the effects of US and PMB (alone and combined) on U-251 MG GBM and A431 epidermoid carcinoma spheroids under different conditions. The synergistic treatment of US- and PMB-induced tumor sphere cell death in a time-, dose-, treatment frequency-, and reactive oxygen species dependent manner, while multiple treatments augmented this effect. Synergistic treatments significantly reduced three-dimensional GBM spheroid regrowth and cell proliferation while inducing cytotoxicity, spheroid shrinkage, and damage to the tumor microenvironment. PMB-induced cytotoxicity throughout the tumor sphere, likely via long-lived reactive oxygen and nitrogen species (H2O2, NO2-, and NO3-) and other reactive species. Appetizer-utilizing plasma microbubbles and ultrasound in the treatment of glioblastoma (GBM) tumor spheroids effectively induces cell death in a manner dependent on time, dose, treatment frequency, and reactive oxygen species levels. The combined approach significantly diminishes the regrowth and proliferation of three-dimensional GBM spheroids while promoting cytotoxicity and spheroid shrinkage. Additionally, it is observed that multiple treatments are more advantageous compared to a single treatment. image