Preparation Of A Novel Au@CeO₂ Core-shell Nanodrug And Its Application In The Treatment Of Rheumatoid Arthritis

Rheumatoid arthritis（RA）is the most common chronic and destructive arthropathy,which results in long-term synovitis and joint disability.The radical improvement of inflammatory cell infiltration and the resulting disorder in oxygen supply is a fire-new 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@CeO₂is 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.This study provides a potential and attractive nanodrug for RA treatment,and also supplies a new idea for the treatment of CeO₂ in other chronic inflammatory diseases.The specific research contents are as follows:1. Synthesis,characterization and properties of Au@CeO₂ nanodrug.The prepared Au@CeO₂ has good biocompatibility and high temperature response under NIR laser irradiation,producing a temperature of about57.6°C,which has a good photothermal effect.At the same time,the increase of temperature enhances the catalytic performance of Au@CeO₂,accelerating the decomposition of H₂O₂ to generate oxygen.2. Research on the performance of Au@CeO₂ nanodrug in the murine macrophage cell line RAW 264.7.Under 808 nm laser irradiation,Calcein-AM staining shows that the plasma photothermal effect of Au@CeO₂ can effectively kill LPS-induced inflammatory cells.In addition,O32,a hydrogen peroxide probe,detects the photothermal effect of Au@CeO2enhances its catalytic activity,showing significant H₂O₂ decomposition ability in the cells.3. Application of Au@CeO₂ in the treatment of RA model mice.After injection of drugs into the articular cavity,the RA mice are treated for 28days.The experimental results show that RA-induced lesions are improved,and the expression of pro-inflammatory cytokines and hypoxia-inducible factor is effectively repressed under the cooperation of heat and oxygen.Micro-CT images of inflammatory paws intuitively show the prominent effect of Au@CeO₂ on RA treatment.