Effective Cancer Cell Killing by Hydrophobic Nanovoid-Enhanced Cavitation under Safe Low-Energy Ultrasound

Graphical Seeds of success : After accumulation in tumors and endocytosis to lysosomes, mesoporous silica nanoparticles with internal hydrophobic mesopores can act as bubble nucleation seeds responding to low-intensity ultrasound. This drastically amplifies the ultrasonic cavitation effect, a process that can disrupt the lysosomal membrane and release lysosomal proteases, thus leading to cell necrosis. β-Cyclodextrin (β-CD)-capped mesoporous silica nanoparticles with hydrophobic internal nanovoids were prepared and used for effective cancer cell killing in synergistic combination with low-energy ultrasound (≤1.0 W cm −2 , 1 MHz). The water-dispersible nanoparticles with hydrophobic internal nanovoids can be taken up by cancer cells and subsequently evoke a remarkable cavitation effect under irradiation with mild low-energy ultrasound (≤1.0 W cm −2 , 1 MHz). A significant cancer cell killing effect was observed in cancer cells and in a mouse xenograft tumor model treated with the nanoagents together with the low-energy ultrasound, showing a distinct dependence on the concentration of nanoagents and ultrasound intensity. By contrast, an antitumor effect was not observed when either low-energy ultrasound or nanoagents were applied alone. These findings are significant as the technique promises a safe, low-cost, and effective treatment for cancer therapy.