Alternative Activation of Macrophages through Interleukin-13-Loaded Extra-Large-Pore Mesoporous Silica Nanoparticles Suppresses Experimental Autoimmune Encephalomyelitis

Multiple sclerosis (MS) treatment via cytokine-mediated immunomodulation has been hampered by the difficulty with which cytokines can be stably and noninvasively delivered to the central nervous system. Here, we show that interleukin (IL)-13 packaged in extra-large-pore mesoporous silica nanoparticles (XL-MSNs) is protected from degradation and directs the alternative activation of macrophages bothin vitroandin vivo. Furthermore, the noninvasive intranasal delivery of IL-13-loaded XL-MSNs ameliorated the symptoms of experimental autoimmune encephalomyelitis, a murine model of MS, accompanied by the induction of chemokines orchestrating immune cell infiltration. These results demonstrate the therapeutic potential of IL-13-loaded XL-MSNs for MS patients.