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

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.