Enhanced-permeability delivery system for hydroxyl radical-responsive NIR-II fluorescence-monitored thrombolytic therapy

Abstract

Pathological thrombus can cause serious acute diseases that present a significant threat to human health, such as myocardial infarction and stroke. Challenges remain in achieving effective thrombolysis and real-time monitoring of therapeutic effects while minimizing side effects. Herein,a multifunctional nanoplatform (TG-OPDEA@UK/MnO₂-H1080) with enhanced thrombus-permeability was developed to monitor the therapeutic effect of antioxidant-thrombolysis by hydroxyl radical-responsive NIR-II fluorescence imaging. The polyzwitterion poly (oxidized N,N-Diethylaminoethyl methacrylate-co-n-butyl methacrylate) (OPDEA) was prepared as the matrix of nanoparticles to simultaneously loading urokinase (UK) and MnO₂ QDs, as well as NIR-II fluorescent molecule, H-1080. Subsequently, the fibrin targeted peptide CREKA was modified on the surface of the nanoparticles. OPDEA exhibits efficient loading capacity while endowing nanoparticles with the ability to effectively increased penetration depth of UK by 94.1 % into the thrombus, for extensive thrombolysis and fluorescence monitoring. The loaded UK exhibited good thrombolytic effect and greatly reduced the risk of bleeding by 82.6 %. TG-OPDEA@UK/MnO₂-H1080 showed good thrombolytic efficacy and specific thrombus monitoring in the mouse carotid artery thrombosis model induced by ferric chloride (FeCl₃). This work prepares a nanoplatform for thrombolytic therapy and real-time efficacy assessment based on an independent externally forced thrombus penetration delivery strategy.