Ultrasound‐Activated Fe‐Doped Hollow BaTiO ₃ Nanoparticles for Targeted Venous Thrombolysis Via Piezo‐Amplified Fenton Catalysis

Abstract Current thrombolytic drug therapies are challenged by limited circulation time, off‐target effects, and bleeding risks. In this study, multifunctional piezoelectric nanoplatforms are rationally designed for piezoelectric Fenton‐assisted thrombolysis. Piezoelectric hollow barium titanate (hBT) nanoparticles (NPs) are synthesized via template‐assisted etching and Fe‐doping, followed by fucoidan grafting to obtain hBT _3Fe ‐Fu NPs. The hollow structure demonstrated a four‐fold enhancement in piezoelectric response compared to that of solid NPs, and Fe‐doping promoted the formation of oxygen vacancies, regulated the bandgap, and enhanced piezoelectric polarization. Moreover, ultrasound‐triggered piezoelectrons accelerated Fe ³⁺ /Fe ²⁺ transformation, synergistically dissolving thrombi with 88.6% efficiency in vitro. In a venous thrombosis model, fucoidan‐mediated active targeting achieved 2.4‐fold greater NP accumulation at the thrombus site. Integrated piezoelectric‐Fenton therapy resulted in complete thrombus dissolution and vessel recanalization while maintaining < 5% bleeding risk and negligible systemic toxicity. The engineered hBT _3Fe ‐Fu nanoplatform represents a promising non‐pharmacological strategy for safe and effective piezocatalytic thrombolytic therapy.