Ultrasmall Barium Titanate Nanoparticles for Highly Efficient Hypoxic Tumor Therapy via Ultrasound Triggered Piezocatalysis and Water Splitting

作者：Ping Wang, Qingshuang Tang, Lulu Zhang, Menghong Xu, Lihong Sun, Suhui Sun, Jinxia Zhang, Shumin Wang, Xiaolong Liang · 发表于：ACS Nano · 年份：2021 · DOI：10.1021/acsnano.1c00616 · 被引用次数：203 · 研究领域：Nanoplatforms for cancer theranostics、Cancer, Hypoxia, and Metabolism、Cancer, Stress, Anesthesia, and Immune Response

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 (O 2 ) in the tumor microenvironment (TME). However, the level of O 2 in TME is too low to produce enough ROS. Herein, we developed an ultrasmall DSPE-PEG 2000 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 O 2, 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 O 2 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.