Ultrasound-Activated Fe-Doped Hollow BaTiO₃ Nanoparticles for Targeted Venous Thrombolysis Via Piezo-Amplified Fenton...

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 Fe³⁺/Fe²⁺ 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.