Recent Progress in Microenvironment-Responsive Nanodrug Delivery Systems for the Targeted Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that often causes joint pain, swelling, and functional impairments. Drug therapy is the main strategy used to alleviate the symptoms of RA; however, drug therapy may have several adverse effects, such as nausea, vomiting, abdominal pain, diarrhea, gastric ulcers, intestinal bleeding, hypertension, hyperglycemia, infection, fatigue, and indigestion. Moreover, long-term excessive use of drugs may cause liver and kidney dysfunction, as well as thrombocytopenia. Nanodrug delivery systems (NDDSs) can deliver therapeutics to diseased sites with the controlled release of the payload in an abnormal microenvironment, which helps to reduce the side effects of the therapeutics. Abnormalities in the microenvironment, such as a decreased pH, increased expression of matrix metalloproteinases (MMPs), and increased concentrations of reactive oxygen species (ROS), are associated with the progression of RA but also provide an opportunity to achieve microenvironment-responsive therapeutic release at the RA site. Microenvironment-responsive NDDSs may overcome the abovementioned disadvantages of RA therapy. Herein, we comprehensively review recent progress in the development of microenvironment-responsive NDDSs for RA treatment, including pH-, ROS-, MMP-, and multiresponsive NDDSs. Furthermore, the pathological microenvironment is highlighted in detail.