Transformable Peptide Blocks NF-κB/IκBα Pathway through Targeted Coating IκBα against Rheumatoid Arthritis

Rheumatoid arthritis (RA) is an autoimmune disease characterized by destructive effects. Although current therapies utilizing antibodies against inflammatory cytokines have shown some success, the inhibition of a single inflammatory molecule may not suffice to impede the progression of RA due to the intricate pathogenesis involving multiple molecules. In this study, we have developed an intelligent transformable peptide, namely BP-FFVLK-DSGLDSM (BFD). BFD has the ability to self-assemble into spherical nanoparticles in water or in the blood circulation to facilitate their delivery and distribution. When endocytosed into immune cells, BFD can identify and attach to phosphorylation sites on IκBα and in situ transform into a nanofibrous network coating NF-κB/IκBα complexes, blocking the phosphorylation and degradation of IκBα. As a result, BFD enables decreasing expression of proinflammatory mediators. In the present study, we demonstrate that BFD exhibits notable efficacy in alleviating arthritis-related manifestations, such as joints and tissues swelling, as well as bone and cartilage destruction on the collagen-induced arthritis (CIA) rat model. The investigation of intracellular biodistribution, phosphorylation of IκBα, and cytokine detection in culture medium supernatant, joint tissue, and serum exhibits strong associations with therapeutic outcomes. The utilization of transformable peptide presents a novel approach for the management of inflammatory diseases.