Rheumatoid arthritis microenvironment insights into treatment effect of nanomaterials

Rheumatoid arthritis (RA) causes a huge medical burden due to its high morbidity and disability rate. Emerging evidences demonstrate that RA has a tumor-like microenvironment. The RA microenvironment (RAM) is an extremely complex network system formed by the crosstalk of various extracellular matrix factors and a variety of stromal cells. Traditional anti-inflammatory standard therapies are compromised by the buffer barrier from the RAM and can only provide short-term relief to RA. Well-designed nanomaterials have attracted intensive interests to overcome the buffer barrier of RAM thanks to their function to simultaneously interfering with multiple pathogenic factors of RAM. Moreover, nanomaterials can achieve precise treatment far beyond traditional therapies through passive and active targeting of RAM strategies. Recently, significant progress in nanomaterials, medicine, and biology have greatly promoted the development of RAM-based nanomaterials for RA treatment with high therapeutic effect, low side effects. Here, we firstly systematically introduced the unique features, constitutes of the RAM, and emphasized the key role of the vicious circle of reactive oxygen and nitrogen species (RONS) and inflammatory factors in the RA progress. We further comprehensively summarized the treatment strategies and recent significant advances of nanomaterials for RA treatment. Finally, we put forward the challenges to clinical application of nanomaterials based on RAM, and discussed the future research direction of RA treatment.