Solvothermal synthesis of Nb-doped TiO₂ nanoparticles with enhanced sonodynamic effects for destroying tumors

Titania (TiO₂) nanomaterials have been proved to be biocompatible sonosensitizers for sonodynamic therapy (SDT) of various cancer cells, while they suffer from weak sonodynamic effects due to fast combination of excited carriers. In this work, to improve the therapeutic efficiency, we prepared PEGylated Nb-doped TiO₂ (TiO_2- :Nb) nanoparticles by a simple solvothermal method and a subsequent surface modification process. The TiO_2- :Nb nanoparticles exhibited an average size of 11 nm and a polydisperse index of 0.12. The Nb doping had no obvious effect on the phase of TiO₂ matrixes but released electrons to the conduction band of TiO₂, resulting in high concentrations of deficiencies. As a result, the TiO_2- :Nb nanoparticles exhibited a higher efficiency of singlet oxygen (¹O₂) generation than that of pure TiO₂ nanoparticles upon ultrasound irradiation. Importantly, the TiO_2- :Nb nanoparticles had high biocompatibility similar to pure TiO₂ nanoparticles, while they could efficiently produce cytotoxic ¹O₂ to destroy cancer cells in vitro in comparison to the partially destroyed cancer cells by pure TiO₂ nanoparticles upon ultrasound irradiation. More importantly, the TiO_2- :Nb nanoparticles displayed obvious tumor cellular injury in tumor-bearing mice in vivo through high SDT effects. Therefore, the synthesized PEGylated TiO_2- :Nb nanoparticles in this study exhibited higher therapeutic effects of SDT than that of the pure TiO₂ nanoparticles, and the doping strategy would provide some insights for tuning traditional weak sonosensitizers into efficient ones.