Biomimetic nanoparticles for effective Celastrol delivery to targeted treatment of rheumatoid arthritis through the ROS-NF-κB inflammasome axis

• Published in: International immunopharmacology 2024-04, Vol.131, p.111822-111822, Article 111822
• Main Authors: Wang, Bo, Shen, Jiquan, Wang, Xinggao, Hou, Ruixing
• Format: Article
• Language: English
• Subjects: Biomimetic Nanoparticles; Celastrol; Leukosome; NF-κB; Rheumatoid arthritis; ROS sensitive
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2024.111822

•Leukosomes had high drug loading and encapsulation efficiency, high stability, and long circulation time.•Leukosomes enabled the selective and effective delivery of celastrol to inflamed tissues, increased drug concentration in affected areas, reduced systemic toxicity of celastrol.•Cel@LEUKO can inhibit the inflammatory response of LPS-induced RAW264.7 cells and MH7A cells through the inhibition of ROS-NF-κB pathway.•Cel@LEUKO reduced clinical symptoms, inflammatory infiltration, serum inflammatory factors and bone erosion in CIA rats. Previous study has indicated that Celastrol (Cel) has various physiological and pharmacological effects, including antibacterial, antioxidant, pro-apoptotic, anticancer and anti-rheumatoid arthritis (RA) effects. However, low water solubility, low oral bioavailability, narrow treatment window, and high incidence of systemic adverse reactions still limit the further clinical application of Cel. Here, aiming at effectively overcome those shortcomings of Cel to boost its beneficial effects for treating RA, we developed the leukosome (LEUKO) coated biomimetic nanoparticles (NPs) for the targeted delivery of Cel to arthritis injury area in RA. LEUKO were synthesized using membrane proteins purified from activated J774 macrophage. LEUKO and Cel-loaded LEUKO (Cel@LEUKO) were characterized using dynamic light scattering and transmission electron microscopy. Our results demonstrated that Cel@LEUKO can inhibit the inflammatory response of lipopolysaccharide (LPS) induced mouse monocyte macrophage leukemia cells (RAW264.7 cells) and human rheumatoid arthritis synovial fibroblasts (MH7A) cells through the inhibition of reactive oxygen species (ROS)-NF-κB pathway. In addition, research has shown that LEUKO effectively targets and transports Cel to the inflammatory site of RA, increased drug concentration in affected areas, reduced systemic toxicity of Cel, and reduced clinical symptoms, inflammatory infiltration, bone erosion, and serum inflammatory factors in collagen-induced arthritis (CIA) rats.