Shear Stress-Triggered Piezo-Photocatalytic Thrombolysis, Self-Luminescent Thrombus Imaging, and Recurrence Prevention.

Thrombotic diseases continue to pose substantial global harm, with high morbidity and mortality rates. Existing theranostic systems for thrombosis face significant risks such as bleeding complications, rapid clearance of therapeutic and imaging agents, and recurrence of thrombi. To overcome these challenges, we have developed a shear stress-triggered thrombosis diagnosis and treatment system, which is expected to achieve site-specific thrombolysis, shear-responsive imaging, and recurrence inhibition. Specifically, tetrakis(4-carboxyphenyl) porphyrin-zinc complexes (ZnTCPP) were anchored on piezoelectric barium titanate (BT) fiber rods (FRs). Luminol and Arg-Gly-Asp (RGD) peptides were then grafted to ZnTCPP, followed by the coordination of remaining carboxyl groups with Zn2+, resulting in the formation of BT@TcLuR/Zn FRs. The sharply elevated shear stress at the thrombus sites triggers piezocatalysis on the porous BT FRs, facilitating the generation of reactive oxygen species (ROS) that oxidize luminol to produce chemiluminescence and further activate ZnTCPP photocatalysis. The excited ZnTCPP forms a heterojunction with BT, enhancing piezo-photocatalytic thrombolysis and enabling self-luminescent thrombus imaging without the need for external light excitation. In a carotid thrombosis model, RGD-mediated targeting increases the luminescent intensity of the thrombus by 5.4-fold, and the integration of clot targeting with piezo-photocatalytic ROS generation significantly improves thrombolysis capacities, resulting in almost complete thrombus dissolution. Efficient clot removal exposes the endothelial layer, while the sustained release of coordinated Zn2+ from FRs promotes re-endothelialization, effectively inhibiting thrombus recurrence within the 10-day observation period. Therefore, this study presents a shear stress-activated theranostic strategy that enables site-specific piezo-photocatalytic thrombolysis, self-luminescent thrombus imaging, and inhibition of thrombus recurrence via endothelial repair.