Comparison Of Therapeutic Effects Of Gold Nano-drug On Rheumatoid Arthritis

Rheumatoid arthritis(RA)is a chronic autoimmune disease characterized by synovial inflammation and progressive cartilage and bone damage.The disease occurs in small joints such as hands,wrists,and feet.Repeated attacks can cause joint swelling and pain,which in turn leads to destruction of cartilage and bone,causing joint deformities and eventually varying degrees of disability.Since the pathogenesis of RA has not been fully clarified,the current treatment strategy is to use the anti-rheumatic drug(DMARDs)to alleviate inflammation,relieve pain,inhibit disease activity,prevent joint injury,and slow disease progression.Although these drugs are effective,but,long-term administration may cause serious systemic complications including stomatitis,alopecia,infection,hepatotoxicity and myelosuppression.Therefore,it is apparent that there is a need to find a new and inexpensive anti-rheumatic drug that can be widely used for the treatment of RA.In our previous studies,we found that Au clusters using glutathione as a template(GACs)produced profound anti-inflammatory effects in vitro on lipopolysaccharide(LPS)-induced inflammation in murine macrophage RAW 264.7 cells and in vivo type II collagen-induced rat RA.In the study,we examined whether the template for Au cluster synthesis has an effect on its anti-inflammatory effect,and whether Au nanoparticle with the larger particle size also produces the same anti-inflammatory effect.We synthesized Au clusters with bovine serum albumin(BSA)as template(BACs),Au clusters with glutathione(GSH)as template(GACs),and Au nanoparticles with glutathione as template(GANs),respectively,compared their anti-inflammatory effects in vitro and in vivo.The particle sizes of BACs,GACs and GANs are 2.4±0.4 nm,2.45±0.15 nm and 25±5 nm,respectively.The gold nanoclusters can emit strong orange fluorescence,and the nanoparticles can not produce fluorescence.Three Au nanomaterials can inhibit the production of lipopolysaccharide(LPS)-induced proinflammatory mediator and prevent type II collagen-induced rat RA.However,although the three Au nanomaterials produced similar anti-inflammatory effects,the GANs with larger particle sizes were less stable in vivo and deposited in the peritoneum after intraperitoneal injection,resulting in poor absorption in vivo.BACs showed higher liver accumulation due to the larger molecular weight of the outer shell.Therefore,we believe that GACs are potential reliable nano-drug for the treatment of RA.