Bismuth sulfide-titania heterostructure used for photothermal amplified sonodynamic therapy against hypoxic tumor

Hypoxia and electron-hole recombination are two obstacles limiting sonodynamic therapeutic efficacy against cancer. Herein, bismuth sulfide (Bi₂S₃)-titania (TiO₂) heterostructure is designed based on the excellent photothermal property of Bi₂S₃, which could improve intratumor oxygen content through increasing blood flow with the help of near infrared light. Bi₂S₃-TiO₂ heterostructure nanoparticles (NPs) present similar photothermal performance to Bi₂S₃ NPs, while Bi₂S₃-TiO₂ NPs show higher reactive oxygen species (ROS) generating ability than Bi₂S₃ NPs under ultrasonic irradiation. <i>In vitro</i> assessments proved that Bi₂S₃-TiO₂ NPs could produce heat and ROS to damage mitochondrial, leading to cell death due to their synergetic photothermal and sonodynamic performances. After being administrated into tumor, Bi₂S₃-TiO₂ NPs can effectively improve oxygen content at 8 h post 808 nm laser irradiation. The tumor growth inhibition rate of Bi₂S₃-TiO₂ NPs with 808 nm laser or ultrasound irradiation is 77.49 ± 3.96 % and 63.64 ± 2.2.7 %, respectively, while it reaches up 88.82 ± 3.98 % when 808 nm laser and ultrasound are applied in sequence, proving the photothermal amplified sonodynamic therapeutic efficacy against hypoxic tumor. As a result, the design of Bi₂S₃-TiO₂ heterostructure NPs realizes photothermal amplified sonodynamic therapy, providing a potential strategy for treating hypoxic tumors.