BaTiO₃@Au nanoheterostructure suppresses triple-negative breast cancer by persistently disrupting mitochondrial energy metabolism

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.