Abnormal metabolism has become a potential target for highly malignant and invasive triple-negative breast cancer (TNBC) due to its relatively low response to traditional therapeutics. The existing metabolic interventions demonstrated unsatisfactory therapeutic outcomes and potential systemic toxicity, resulting from the metabolic instability and limited targeting ability of inhibitors as well as complex tumor microenvironment. To address these limitations, here we developed a robust pyroelectric BaTiO₃@Au core–shell nanostructure (BTO@Au) to selectively and persistently block energy generation of tumor cells. Stimulated by near-infrared (NIR) laser, the Au shell could generate heat to activate the BaTiO₃ core to produce reactive oxygen species (ROS) regardless of the constrained microenvironment, thus prominently inhibits mitochondrial oxidative phosphorylation (OXPHOS) and reduces ATP production to induce TNBC cell apoptosis. The therapeutic effects have been well demonstrated in vitro and in vivo, paving a new way for the development of metabolic interventions.

Breast cancer is a common malignancy in women with disappointing prognosis especially the triple-negative subtype. Recently, nanomedicine becomes a promising therapeutic strategy for breast cancer, such as platinum nanoparticles (PtNPs). Despite the promising anticancer effects of PtNPs, the safety of PtNPs remains to be fully evaluated. Herein, a series of cell and animal experiments demonstrate that PtNPs facilitate breast cancer metastasis by damaging the vascular endothelial barrier. PtNPs disrupt endothelial cell proliferation, migration and tube-like structure formation, destruct endothelial adhesions junctions and induce endothelial barrier leakinessin vitro most likely by stimulating intracellular reactive oxygen species (ROS) generation and altering the expression and conformation of endothelial junctional proteins, thus promoting intravasation and extravasation of the implanted 4T1 breast cancer cells and leading to cancer metastasis in female BALB/c nude micein vivo. In addition, smaller PtNPs (5 nm) are more potent than larger PtNPs (70 nm) in exerting the above effects. The study provides the first evidence that PtNPs can promote breast cancer metastasis by damaging endothelial barrier. The unexpected detrimental effects of PtNPs should be considered in future nanomedicine designs for the treatment of breast cancer.