In Vitro Sonodynamic Therapeutic Effect of Polyion Complex Micelles Incorporating Titanium Dioxide Nanoparticles

Titanium dioxide nanoparticles (TiO(2) NPs) can act as sonosensitizers, generating reactive oxygen species under ultrasound irradiation, for use in sonodynamic therapy. For TiO(2) NPs delivery, we prepared polyion complex micelles incorporating TiO(2) NPs (TiO(2) NPs-PIC micelles) by mixing TiO(2) NPs with polyallylamine bearing poly(ethylene glycol) grafts. In this study, the effects of polymer composition and ultrasound irradiation conditions on the sonodynamic therapeutic effect toward HeLa cells were evaluated experimentally using cell viability evaluation, intracellular distribution observation, and a cell staining assay. TiO(2) NPs-PIC micelles with widely distributed features induced a significant decrease in cell viability under ultrasound irradiation. Furthermore, prolonging the irradiation time killed cells more effectively than did increasing the ultrasound power. The combination of TiO(2) NP-PIC micelles and ultrasound irradiation was confirmed to induce apoptotic cell death.