Macrophage Membrane‐Coated Carbon Nanozymes for Targeted Drug Delivery and NIR‐Responsive Synergistic Therapy in Rheumatoid Arthritis

Abstract Rheumatoid arthritis (RA) remains a therapeutic challenge due to the persistently dysregulated synovial microenvironment that drives chronic inflammation and treatment resistance. Herein, a biomimetic nanoplatform composed of macrophage membrane (MM)‐coated porous carbon nanospheres (MM@PCNSs) is developed for synergistic immunomodulation and targeted iguratimod (IGU) delivery in RA therapy. The PCNS core integrates multi‐enzyme mimetic activities for efficient reactive oxygen species (ROS) scavenging and supports high drug loading with pH/NIR‐responsive release. Biomimetic macrophage membrane cloaking enables inflammation‐targeted delivery and in situ neutralization of cytokines. In vitro, MM@PCNSs/IGU effectively reduced oxidative stress and inhibited pro‐inflammatory cytokines. In vivo, NIR‐activated MM@PCNSs/IGU significantly alleviated synovial inflammation, reduced joint destruction, and improved clinical scores in collagen‐induced arthritis (CIA) mice. This multifunctional nanoplatform integrates targeted delivery, redox regulation, and immune reprogramming to overcome limitations of conventional therapies, offering a promising strategy for restoring synovial homeostasis and achieving durable remission in RA.