Hypoxia in a solid tumor microenvironment (TME) can lead to the overexpression of
hypoxia-inducible factor-1α (HIF-1α), which correlates to
tumor metastasis.
Reactive oxygen species (ROS) induced
tumor cell apoptosis is becoming a promising method in
tumor treatment. Currently, the ROS generating systems, e.g., photodynamic treatment and sonodynamic treatment, highly depend on
oxygen (O2) in the tumor microenvironment (TME). However, the level of O2 in TME is too low to produce enough ROS. Herein, we developed an ultrasmall
DSPE-PEG2000 coated
barium titanate nanoparticle (P-BTO) for
tumor treatment based on ultrasound triggered piezocatalysis and water splitting. Interestingly, irradiated by ultrasound, the surface of ultasmall P-BTO nanoparticles produced imbalance charges, which induced a cascade of redox reaction processes to simultaneously generate ROS and O2, the latter one was hardly generated in large-sized
barium titanate nanoparticles. The as-synthesized P-BTO reached the highest accumulation in the
tumor site at 4 h after
intravenous injection. The results showed that the produced O2 significantly alleviated the
hypoxia of TME to down-regulate the expression of HIF-1α, and the produced ROS can efficiently kill
tumor cells. Moreover, the
tumor metastasis was also inhibited, providing a different way to treat
triple-negative breast cancer, which was easily metastatic and lacked effective treatments in the clinic.