LAUSR

During cerebral ischemia‐reperfusion (I‐R) injury, the infiltration of monocyte/macrophages (Mo/Mφ) into the ischemic penumbra causes inflammatory damage but also regulates tissue repair in the penumbra. The regulation and balance of Mo/Mφ polarization is considered as a potential therapeutic target for treating cerebral I‐R injury. Herein, these findings demonstrate that glabridin (Gla)‐loaded nanoparticles (i.e., NPGla‐5k) can effectively inhibit M1‐polarization and enhance M2‐polarization of Mo/Mφ. Positron emission tomography (PET) imaging shows that NPGla‐5k can selectively accumulate in the spleen following intravenous injection. Spleen‐targeted Cy5‐NPGla‐5k can co‐localize with peripheral macrophages in the penumbra at 24 h after tail‐vein injection. Interestingly, NPGla‐5k treatment can reduce inflammatory damage, protect dying neurons, and improve nervous system function. The protective effect of spleen‐targeted NPGla‐5k against cerebral I‐R injury in mice encourages an exploration of their use for clinical treatment of patients with cerebral I‐R injury.