V-TiO2 nanospindles with regulating tumor microenvironment performance for enhanced sonodynamic cancer therapy

Abstract

Sonodynamic therapy, with advantages in large tissue penetration depth and great controllability, is a promising type of non-invasive cancer treatment method. Developing sonosensitizers with high reactive oxygen species (ROS) quantum yield and the ability to regulate tumor microenvironment to achieve enhanced performances in sonodynamic therapy would thus be rather attractive. Herein, vanadium (V) doped TiO2 (V-TiO2) nanospindles with glutathione-depleting properties are fabricated for enhanced sonodynamic cancer therapy. Due to doping of the V element, the bandgap of V-TiO2 nanospindles is reduced, increasing the efficiency of ultrasound-triggered ROS production compared to that of pure TiO2 nanoparticles. More interestingly, the doping of V also makes V-TiO2 nanospindles an effective Fenton-like agent, which can catalyze the generation of highly toxic hydroxyl radicals (•OH) from endogenous H2O2 in the tumor, thus enabling cancer-killing through chemodynamic therapy. In addition, the V doping also endows V-TiO2 nanospindles with the function of glutathione depletion, further amplifying the oxidative stress generated by chemodynamic-sonodynamic therapy. In vitro cell experiments and in vivo animal experiments demonstrate that V-TiO2 nanospindles can effectively kill cancer by the combined chemodynamic-sonodynamic therapy, significantly improving the tumor treatment outcomes. Importantly, V-TiO2 with the ultrasmall spindle morphology can be quickly excreted from the body, without causing any long-term toxicity. This work illustrates that doping TiO2 with other special elements is a meaningful strategy to fabricate nanostructures with interesting functions useful in biomedicine.