TiO2 nanocrystals were synthesized from hydrothermal reaction of tetrabutyl titanate and acetic acid, and then reacted with Bi(NO3)3 to prepare Bi2O3/TiO2 nanoparticles (BTH), which was further coated with polydopamine (PDA) to obtain BTH@PDA nanoparticles (BTP). The BTP nanoparticles were characterized by TEM, XRD and XPS for analyses on morphology and composition, and evaluated through biosafety test, cytotoxicity assay, cellular uptake assay and reactive oxygen species (ROS) staining, respectively, on their biosafety, biocompatibility and the ability of ROS generation. The results indicated that BTP exhibited a fusiform shape, with the longest side having a particle size of (125.18±14.66) nm, and a Zeta potential of (–4.17±0.33) mV. BTP suspension showed no obvious toxicity towards L929 and 4T1 cells at a mass concentration significantly above normal treatment concentration (300 μg/mL). Meanwhile, BTP could enhance the therapeutic outcome of radiotherapy and effectively generate ROS in response to ultrasound. After co-treatment by ultrasound and X ray, BTP could reduce the survival rate of 4T1 cells to 34.3%. The cellular uptake of BTP by 4T1 cells was time-dependent, with the maximum uptake occurring around 12 h. © 2024 Fine Chemicals. All rights reserved.