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

Abstract

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 (TiO2−x:Nb) nanoparticles by a simple solvothermal method and a subsequent surface modification process. The TiO2−x: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 TiO2−x:Nb nanoparticles exhibited a higher efficiency of singlet oxygen (1O2) generation than that of pure TiO2 nanoparticles upon ultrasound irradiation. Importantly, the TiO2−x: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 TiO2−x:Nb nanoparticles displayed obvious tumor cellular injury in tumor-bearing mice in vivo through high SDT effects. Therefore, the synthesized PEGylated TiO2−x: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.