Shear Stress-Triggered Theranostic Nanoparticles for Piezoelectric-Fenton-Photodynamic Thrombolysis and Endogenous Thrombus Imaging

Thrombus therapy is challenged by potential bleeding risk of thrombolytic agents, and external irradiation is usually needed in thrombus imaging. Herein, highly efficient theranostic platforms are designed for piezoelectric-Fenton-photodynamic thrombolysis and endogenous thrombus imaging in response to the elevated shear stress at the thrombus site. Piezoelectric tetragonal barium titanate (tBT) nanoparticles (NPs) are coated with Fe 3+ -coordinated metal-organic frameworks (MOFs), followed by inoculation of chlorin e6-luminol conjugates and heparin absorption to obtain theranostic tBT@MOF CL /Hep NPs. Shear stress-induced piezopotential on NPs accelerates Fe 3+ /Fe 2+ transformation to deplete MOF layers, activates Fenton reaction and produces reactive oxidative species (ROS) for non-pharmacological thrombolysis. In the meantime, the site-specific ROS generation oxidizes luminol and the chemiluminescent resonance energy transfer with chlorin e6 generates red fluorescence for thrombus imaging without using external light irradiation. After intravenous injection into a carotid artery thrombosis model, the heparin-mediated thrombus targeting yields 6.5-fold higher luminescent intensity at the thrombus site. Thrombi in the carotid arteries are almost completely dissolved with integration of piezoelectric dynamic therapy, piezopotential-enhanced Fenton reaction, and chemiluminescence-excited photodynamic therapy, while causing no haematologic and histopathologic abnormality. This study demonstrates a concise strategy to generate shear stress-responsive built-in piezoelectric potentials, site-specific non-pharmacological thrombolysis, self-illuminating, and stenosis degree-adaptable thrombus imaging.