Oxygen-deficient titanium dioxide-loaded black phosphorus nanosheets for synergistic photothermal and sonodynamic cancer therapy

Malignant tumors, particularly those located in deep tissues, have always been a grievous threat to human health. Sonodynamic therapy (SDT) has recently attracted great attention due to deep tissue penetration. However, the lack of effective sonosensitizers and the poor therapeutic efficacy severely limit their wider use. Herein, dual-functionalized black phosphorus nanosheets (BP@PEI-PEG, i.e., PPBP) integrating black oxygen-deficient titanium dioxide particles (B-TiO2) were successfully constructed (PPBP-B-TiO2) for synergistic photothermal (PTT)/sonodynamic therapy. In these nanocomposites, black titanium dioxide can enhance the separation of electrons (e-) and holes (h+) due to the oxygen-deficient structure and significantly improves the production of reactive oxygen species (ROS) for SDT, while the BP nanosheets endow the nanocomposites with a higher photothermal conversion capability for photothermal therapy (η = 44.1%) which can prolong the blood circulation and improve the O2 supply. In vivo experiments prove that PPBP-B-TiO2 nanocomposites exhibited outstanding tumor inhibition efficacy and excellent biocompatibility. This work provides a prospective platform for combined photothermal/sonodynamic cancer therapy.