Recent years have witnessed a surge in the development of nanomedicine for combating RA, with the purpose of bypassing the defects of the current treatments.
Therefore, novel therapeutic strategies for RA treatment are still urgently warranted. The biological agents are also developed to prevent joint destruction by suppressing the cytokines' level, but the therapeutic benefits are not as good as expected, accompanied by serious risks such as tuberculosis reactivation and serious infections. While they can improve the symptoms and slow arthritis progression, high dosage and frequent administration are often required to obtain satisfactory efficacy, which inevitably cause untoward side-effects. Currently, RA is still an incurable disease, and there are three classes of medications commonly used in clinic, i.e., non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCs), and disease-modifying anti-rheumatic drugs (DMARDs).
The disease is characterized by progressive inflammation and persistent synovitis, leading to bone and cartilage destruction, functional incapability, and ultimately disability. Rheumatoid arthritis (RA) is a type of chronic auto-immune disorder that affects ~1% of the adult population. This work declares the first example of using bio-active nanoparticles for RA treatment without loading any drugs, and highlights the potential of FA-AgNPs for targeted RA therapy via simultaneous M1 macrophage apoptosis and M1-to-M2 macrophages re-polarization. After treatment, FA-AgNPs could be gradually cleared from the body mainly via feces without tissue accumulation, and did not show any appreciable long-term toxicity. This nano-system could passively accumulate into inflamed joints, permit potent anti-inflammatory activity, and impose strong therapeutic efficacy in mice RA models with high biosafety.
#Silver nanoparticles caprine arthritic encephalitis series
After entering cells, FA-AgNPs dissolved and released Ag + in response to intracellular glutathione (GSH), which is the key element to exert a series of anti-inflammatory functions, such as M1 macrophages apoptosis and reactive oxygen species (ROS) scavenging to facilitate M2 macrophages polarization, both of which contributed to RA treatment. The AgNPs was facilely prepared, PEGylated and modified with FA to realize M1 macrophages targeting delivery via folate receptor overexpressed on M1 macrophages surface. We herein developed folic acid modified silver nanoparticles (FA-AgNPs) that can actively deliver into M1 macrophages to synergistically induce M1 macrophages reduction and M2 macrophages polarization for effective RA treatment. To relief synovial inflammation, M1 macrophages must be eliminated or switched to anti-inflammatory M2 phenotype.
Infiltration of inflammatory cells, especially the M1 macrophages that secrete various types of inflammation cytokines, play crucial roles in the pathogenesis of rheumatoid arthritis (RA).