Ultrasound-Driven Piezoelectric Heterostructures Block Early Atherosclerotic Plaques Progression

Atherosclerosis (AS), marked by lipid buildup and chronic inflammation in arteries, leads to major cardiovascular events. Macrophages contribute to AS by engulfing low-density lipoproteins, forming foam cells, and driving inflammation that promotes plaque growth and instability. The emerging piezocatalytic therapy uses piezoelectric materials to generate radicals that target inflammation-related macrophages for AS treatment, but the conventional materials suffer from low radical yield, substantially limiting clinical use. In this study, the construction of piezoelectric BaTiO₃/Ta₄C₃ MXene heterostructured nanosheets (BTOMX NSs) is reported for achieving enhanced piezoelectric AS treatment by blocking early atherosclerotic plaque progression. The composite BTOMX NSs feature high electron-hole separation efficiency due to their narrowed bandgap and high surface potential under ultrasound irradiation, enabling more effective radical generation by piezocatalytic effects. Especially, these biocompatible piezoelectric nanosheets accumulate in plaques and are efficiently internalized by macrophages, where they generate radicals under ultrasound stimulation, ultimately triggering macrophage apoptosis and interrupting plaque progression. In ApoE^-/- mice, the BTOMX NSs remove lesional macrophages, reduce lipid accumulation, and mitigate inflammation, decreasing plaque burden from 21.42% to 9.04%. Taken together, this work provides a paradigm for enhancing BaTiO₃-based piezocatalytic performance by heterostructure construction, demonstrating an efficient, noninvasive, and safe therapeutic approach for treating early-stage AS.