Inflammation‐Targeted Biomimetic Nano‐Decoys via Inhibiting the Infiltration of Immune Cells and Effectively Delivering Glucocorticoids for Enhanced Multiple Sclerosis Treatment

Abstract Excessive infiltration of neutrophil and inflammatory cytokines accumulation as well as the inadequate delivery of drugs to the targeted site are key pathological cascades in multiple sclerosis (MS). Herein, inflammation‐targeting biomimetic nano‐decoys (TFMN) is developed that inhibit the infiltration of immune cells and effectively deliver glucocorticoids to lesions for enhanced MS treatment. Nano‐decoys encapsulated with the glucocorticoid methylprednisolone (MPS) are prepared by coating neutrophil membrane (NM) on nanoparticles formed by the self‐assembly of tannic acid and poloxamer188/pluronic68. Benefiting from the natural inflammation‐targeting ability of activated neutrophil membranes, TFMN can target the lesion site and prevent neutrophils infiltration by adsorbing and neutralizing elevated neutrophil‐related cytokines, subsequently modulating the inflammatory microenvironment in experimental autoimmune encephalomyelitis mice. TFMN exhibits a strong antioxidant capacity and scavenged excessive reactive oxygen species to enhance neuronal protection. Furthermore, at the inflammation site, perforin, discharged by cytotoxic T‐lymphocytes, triggered the controlled release of MPS within the TFMN through perforin‐formed pores in the NM. Simultaneously, this mechanism protected neurons from perforin‐induced toxicity. The MPS liberated at the targeted site achieves optimal drug accumulation, thereby enhancing therapeutic efficacy. In conclusion, the innovative system shows potential for integrating various therapeutic agents, offering a novel strategy for CNS disorders.