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However, the available treatment options targeting both inflammatory and proliferative FLS are limited. Herein, this work presents three covalent organic frameworks (COFs) photothermal composite systems modified with multi\u2010armed polyethylene glycols (PEG) for the treatment of RA. These systems exhibit a dual response under low pH and high reactive oxygen species (ROS) conditions at the site of inflammation, with a specific focus on delivering the protein drug ribonuclease A (RNase A). Notably, molecular docking studies reveal the interaction between RNase A and NF\u2010\u03baB p65 protein, and Western blotting confirm its inhibitory effect on NF\u2010\u03baB activity. In vitro and in vivo experiments verify the significant reduction in joint swelling and deformities in adjuvant\u2010induced arthritis (AIA) rats after treatment with RNase A delivered by multi\u2010armed PEG\u2010modified COF ligands, restoring joint morphology to normal. These findings underscore the promising therapeutic potential of COFs for the treatment of RA, highlighting their unique capabilities in addressing both inflammatory and proliferative aspects of the disease and expanding the scope of biomedical applications for COFs.<\/jats:p>","DOI":"10.1002\/adhm.202401744","type":"journal-article","created":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T13:34:16Z","timestamp":1718631256000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Responsive Multi\u2010Arm PEG\u2010Modified COF Nanocomposites: Dynamic Photothermal, pH\/ROS Dual\u2010Responsive, Targeted Carriers for Rheumatoid Arthritis Treatment"],"prefix":"10.1002","volume":"13","author":[{"given":"Saisai","family":"Ge","sequence":"first","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Anhui Medical University  Hefei 230032 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