A targeted activatable NIR-II nanoprobe for positive visualization of anastomotic thrombosis and sensitive identification of fresh fibrinolytic thrombus

Anastomotic thrombosis prevalently causes anastomosis failure, accompanied with ischemia and necrosis, the early diagnosis of which is restricted by inherent shortcomings of traditional imaging techniques in clinic and lack of appropriate prodromal biomarkers for thrombosis initiation. Herein, a fresh thrombus-specific molecular event, protein disulfide isomerase (PDI) is innovatively chosen as the activating factor, and a thrombosis targeting and PDI-responsive turn-on near infrared II (NIR-II) fluorescence nanoprobe is firstly developed. The supramolecular complex-based nanoprobe IR806-PDA@BSA-CREKA is fabricated by assembling NIR-II emitting cyanine deriva-tive IR806-PDA with bovine serum albumin (BSA), which could ameliorate the stability and pharmacokinetics of the nanoprobe, addressing the contradiction in the balance of brightness and biocompatibility. The NIR-II-off nanoprobe exhibits robust turn-on NIR-II fluorescence upon PDI-specific activation, in vitro and in vivo. Of note, the constructed nanoprobe demonstrates superior photophysical stability, efficient fibrin targeting peptide -derived thrombosis binding and a maximum signal-to-background ratio (SBR) of 9.30 for anastomotic throm-bosis in NIR-II fluorescent imaging. In conclusion, the exploited strategy enables positive visualized diagnosis for anastomotic thrombosis and dynamic monitoring for thrombolysis of fresh fibrinolytic thrombus, potentially contributes a novel strategy for guiding the therapeutic selection between thrombolysis and thrombectomy for thrombosis treatment in clinic.

Automated summary

A new nano-probe targeting thrombosis with activated near infrared II fluorescence has been developed using protein disulfide isomerase (PDI) as an activator. This probe demonstrates excellent photophysical stability, efficient fibrin targeting, and a high signal-to-background ratio, providing a visualized diagnosis and monitoring for thrombolysis in blood clot treatment.