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

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.