Multi-enzyme mimetic iridium nanozymes-based thrombus microenvironment-modulated nanoplatform for enhanced thrombolytic therapy

Intravenous injection of thrombolytic drugs is the most feasible strategy for the clinical treatment of thrombotic diseases, however, its applications are yet limited by narrow therapeutic index, short half-life, and hemorrhagic risk. Inspired by the excessive ROS and inflammatory factors at the thrombus site, we manufactured a thrombus microenvironment-modulated nanosystem, which achieved the targeted delivery of thrombolytic drugs and ROS scavenging agents. Ir monomers (Ir-PVP) with enzyme-mimetic activity were prepared and then wrapped with lumbrokinase (LK) by HA materials of thrombo-inflammatory affinity, forming multifunctional thrombolytic agents Ir-LK@HA. Ir-LK@HA could prolong the biological half-life of LK and target the thrombus site to release LK with reduced bleeding risk. Moreover, Ir-NPs, as both CT imaging contrast agent and ROS scavenger, not only allowed us to observe the progression of thrombolytic treatment through CT imaging in real time, but also played an important role in elimination of excessive ROS at thrombus site. Taken together, the in vitro and in vivo experiments illustrated that Ir-LK@HA with CT function displayed an excellent efficiency in thrombolysis, anti-inflammation and ROS scavenging. Our work may encourage further exploration of thrombus microenvironment-modulated theranostic platforms.