Crystalline carbon antioxidase mimics enhancing innate anti-inflammatory immunity for the treatment of rheumatoid arthritis

Abstract

It is imperative to restore the aberrant anti-inflammatory immunity in inflamed lesions along with suppression of oxidative stress for the effective therapy of the autoimmune disease rheumatoid arthritis (RA). Herein, carbon antioxidase mimics (CAMs) as an artificial superoxide dismutase are designed and modulated in intracellular function through control over their crystal phases for RA treatment. Crystalline CAM (crys-CAM) with superior catalytic activity and cell permeability can enhance the innate immunity provided by intracellular antioxidation and anti-inflammation functions in RA lesions. Experiments and simulations reveal that crys-CAM can catalytically scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS) through a proton-transfer redox cycle and suppress the secretion of pro-inflammatory cytokines in macrophages. Additionally, crys-CAM activates Nrf2-dependent cellular immunity, leading to a considerable increase in the expression and activity of innate detoxifying and antioxidant enzymes inside cells. Crys-CAM is used in RA mouse models, displaying its promising therapeutic efficacy via the restoration of innate anti-inflammatory responses. The mimetic functions of crys-CAM provide a new approach for the effective therapy of RA and other autoimmune diseases. © 2024 Elsevier B.V.