Biomimetic Immunoregulators for the Multi-Target Inflammation Interruption in Autoimmune Diseases

Cell-free DNA (cfDNA), reactive oxygen species (ROS), and pro-inflammatory cytokines interplay to form a self-amplified inflammatory cascade in autoimmune diseases (AIDs), accounting for the limited efficacy of single-target therapeutic modalities. Herein, biomimetic nanoparticles (NPs), constructed from macrophage membrane (RM)-coated cerium oxide (CeO₂), are developed to concurrently scavenge multiple inflammatory mediators for AID management. Upon systemic administration, the NPs feature long blood circulation and targeted accumulation at the inflamed site. In the inflammatory microenvironment, RM with abundant cytokine receptors neutralizes varieties of pro-inflammatory cytokines, and CeO₂ with nuclease- and antioxidase-like activities scavenges multiple types of ROS. In addition, O₂ bubbles generated from CeO₂-catalyzed H₂O₂ decomposition foster membrane shedding and subsequent CeO₂ exposure for effective cfDNA cleavage. Thus, the NPs effectively interrupt the inflammatory cycle and promote tissue repair in mouse models of AIDs including rheumatoid arthritis and autoimmune hepatitis. This study provides an effective mechanism for the multi-target management of inflammation, which holds profound implications for the treatment of AIDs.