NIR-PTT/ROS-Scavenging/Oxygen-Enriched Synergetic Therapy for Rheumatoid Arthritis by a pH-Responsive Hybrid...

Rheumatoid arthritis (RA) is an inflammatory type of arthritis that causes joint pain and damage. The inflammatory cell infiltration (e.g., M1 macrophages), the poor O₂ supply at the joint, and the excess reactive oxygen species (ROS)-induced oxidative injury are the main causes of RA. We herein report a polydopamine (PDA)-coated CeO₂-dopped zeolitic imidazolate framework-8 (ZIF-8) nanocomposite CeO₂-ZIF-8@PDA (denoted as CZP) that can synergistically treat RA. Under near-infrared (NIR) light irradiation, PDA efficiently scavenges ROS and results in an increased temperature in the inflamed area because of its good light-to-heat conversion efficiency. The rise of temperature serves to obliterate hyper-proliferative inflammatory cells accumulated in the diseased area while vastly promoting the collapse of the acidic-responsive skeleton of ZIF-8 to release the encapsulated CeO₂. The released CeO₂ exerts its catalase-like activity to relieve hypoxia by generating oxygen via the decomposition of H₂O₂ highly expressed in the inflammatory sites. Thus, the constructed CZP composite can treat RA through NIR-photothermal/ROS-scavenging/oxygen-enriched combinative therapy and show good regression of pro-inflammatory cytokines and hypoxia-inducible factor-1α (HIF-1α) in vitro and promising therapeutic effect on RA in rat models. The multimodal nano-platform reported herein is expected to shed light on the design of synergistic therapeutic nanomedicine for effective RA therapy.