Spleen‐Targeted Glabridin‐Loaded Nanoparticles Regulate Polarization of Monocyte/Macrophage (M_o/M_φ) for the Treatment of Cerebral Ischemia‐Reperfusion Injury

Abstract During cerebral ischemia‐reperfusion (I‐R) injury, the infiltration of monocyte/macrophages (M_o/M_φ) into the ischemic penumbra causes inflammatory damage but also regulates tissue repair in the penumbra. The regulation and balance of M_o/M_φ 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., NP_Gla‐5k) can effectively inhibit M1‐polarization and enhance M2‐polarization of M_o/M_φ. Positron emission tomography (PET) imaging shows that NP_Gla‐5k can selectively accumulate in the spleen following intravenous injection. Spleen‐targeted Cy5‐NP_Gla‐5k can co‐localize with peripheral macrophages in the penumbra at 24 h after tail‐vein injection. Interestingly, NP_Gla‐5k treatment can reduce inflammatory damage, protect dying neurons, and improve nervous system function. The protective effect of spleen‐targeted NP_Gla‐5k against cerebral I‐R injury in mice encourages an exploration of their use for clinical treatment of patients with cerebral I‐R injury.