Immuno‐Engineered Nanodecoys for the Multi‐Target Anti‐Inflammatory Treatment of Autoimmune Diseases

Overactivated T cells and overproduced pro-inflammatory cytokines form a self-amplified signaling loop to continuously exacerbate the dysregulated inflammatory response and propel the progression of autoimmune diseases (AIDs). Herein, immuno-engineered nanodecoys (NDs) based on poly(lactic-co-glycolic acid) nanoparticles coated with programmed death-ligand 1 (PD-L1)-expressing macrophage membrane (PRM) are developed to mediate multi-target interruption of the self-promoted inflammatory cascade in AIDs. The PRM collected from IFN-γ-treated RAW 264.7 cells possesses elevated surface levels of adhesion molecule receptors and pro-inflammatory cytokine receptors, and, thus, systemically administered PRM NDs afford higher accumulation level in inflamed tissues and stronger scavenging efficiency toward multiple pro-inflammatory cytokines. More importantly, IFN-γ treatment induces remarkable PD-L1 expression on PRM, thereby allowing PRM NDs to bind membrane-bound programmed death-1 (PD-1) on CD4+ T cell surfaces or neutralize free soluble PD-1, which reconstructs the PD-1/PD-L1 inhibitory axis to suppress CD4+ T cell activation and restore immune tolerance. As such, PRM NDs provoke potent and cooperative anti-inflammatory and immune-suppressive efficacies to alleviate autoimmune damages in Zymosan A-induced arthritis mice and dextran sulfate sodium-induced ulcerative colitis mice. This study provides an enlightened example for the immuno-engineering of cell-membrane-based NDs, rendering promising implications into the treatment of AIDs via multi-target immune-modulation.