Cold beer-inspired multifunctional nanozyme for ischemic stroke with rapid thrombus clearance and long-lasting hydrogen therapy

Abstract

Ischemic stroke is a thrombus-inflammatory disease caused by cerebral vascular blockage. The narrow treatment window presents challenges for timely intervention and neurological recovery. Inspired by cold beer, we developed a multifunctional nanozyme (CREKA-MOF@Pd/H₂-uPA, denoted as CMPd(H)U). After injection, CMPd(H)U efficiently targeted the thrombus and combined with gas therapy to expedite thrombolysis and restore blood flow. Additionally, CMPd(H)U released hydrogen (H₂) to eliminate reactive oxygen species (ROS), thereby mitigating reperfusion injury. Furthermore, CMPd(H)U demonstrated anti-inflammatory and neuroprotective properties by modulating microglial polarization towards the M2 phenotype and inhibiting neuronal pyroptosis. Animal behavioral experiments confirmed the effectiveness of the system in promoting neuromotor function recovery post-stroke.