Rheumatoid arthritis (RA) is an autoimmune disease that often causes progressive joint dysfunction, even disability and death in severe cases. The radical improvement of inflammatory cell infiltration and the resulting disorder in oxygen supply is a novel therapeutic direction for RA. Herein, a near-infrared-absorbing metal/semiconductor composite, polyethylene glycol-modified ceria-shell-coated gold nanorod (Au@CeO2), is fabricated for topical photothermal/oxygen-enriched combination therapy for RA in a mouse model. Upon laser irradiation, the photothermal conversion of Au@CeO2 is exponentially enhanced by the localized surface plasma resonance-induced light focusing. The elevated temperature can not only remarkably obliterate hyperproliferative inflammatory cells gathered in diseased joints but also vastly increase the catalase-like activity of ceria to accelerate the decomposition of H2O2 to produce much oxygen, which relieves hypoxia. Significantly, RA-induced lesions are improved, and the expression of proinflammatory cytokines and hypoxia-inducible factors is effectively repressed under the cooperation of heat and oxygen. Overall, the core/shell-structured Au@CeO2 is a promising nanotherapeutic platform that can well realize light-driven heat/oxygen enrichment to completely cure RA from the perspective of pathogenesis.
Keywords: combined therapy; enhanced catalytic performance; oxygen generation; plasmonic phototherapy; rheumatoid arthritis.