Neutrophil Hitchhiking Biomimetic Nanozymes Prime Neuroprotective Effects of Ischemic Stroke in a Tailored “Burning the Bridges” Manner
Junyan Song, Guang Yang, Yan Song, Zeyu Jiang, Yue Jiang, Yuxia Luan, Wenxiu He
Abstract
Abstract Reperfusion injury of ischemic stroke, characterized by the uncontrolled production of reactive oxygen species (ROS) and inflammatory reactions, continues to present a major problem in clinical treatment. Neutrophils are forerunners to infiltrate cerebral ischemic regions and contribute to reperfusion injury. Herein, this study reports a tailored “burning the bridges” strategy by designing biomimetic nanozymes (D@HPB@SPM NPs) to diminish reperfusion injury of ischemic stroke. D@HPB@SPM NPs are composed of a sialic acid (SA)‐modified platelet membrane shell and a hollow Prussian blue nanoparticle core loaded with Deoxyribonuclease I (DNase I). Due to the unique binding affinity of SA to L‐selectin, which is abundantly expressed in circulating neutrophils, D@HPB@SPM NPs can effectively hitchhike on neutrophils across the blood‐brain barrier into the injured brain parenchyma after intravenous injection. Following this, neutrophils are activated and unleash D@HPB@SPM NPs through producing neutrophil extracellular traps (NETs). D@HPB@SPM NPs not only relieve oxidative stress injury by efficiently scavenging ROS, but also mitigate neutrophil‐induced reperfusion injury by degrading NETs in a manner similar to “burning the bridges”. The encouraging accumulation of D@HPB@SPM NPs to cerebral ischemic regions and their efficient therapeutic efficacy are systematically validated in ischemic stroke rats. This work offers a fresh insight for ischemic stroke treatment.