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Osteoarthritis (OA) is an inflammatory and degenerative joint disease with severe effects on individuals, society, and the economy that affects millions of elderly people around the world. To date, there are no effective treatments for OA; however, there are some treatments that slow or prevent its progression. Polyfunctional nanosystems have many advantages, such as controlled release, targeted therapy and high loading rate, and have been widely used in OA treatment. Previous mechanistic studies have revealed that inflammation and ROS are interrelated, and a large number of studies have demonstrated that ROS play an important role in different types of OA development. In this review article, we summarize third-generation ROS-sensitive nanomaterials that scavenge excessive ROS from chondrocytes and osteoclasts in vivo. We only focus on polymer-based nanoparticles (NPs) and do not review the effects of drug-loaded or heavy metal NPs. Mounting evidence suggests that polyfunctional nanosystems will be a promising therapeutic strategy in OA therapy due to their unique characteristics of being sensitive to changes in the internal environment.

Arthritis is a group of highly prevalent joint disorders, and osteoarthritis (OA) and rheumatoid arthritis are the two most common types. The high prevalence of arthritis causes severe burdens on individuals, society and the economy. Currently, the primary treatment of arthritis is to relieve symptoms, but the development of arthritis cannot be effectively prevented. Studies have revealed that the disrupted balance of enzymes determines the pathological changes in arthritis. In particular, the increased levels of matrix metalloproteinases and the decreased expression of endogenous antioxidant enzymes promote the progression of arthritis. New therapeutic strategies have been developed based on the expression characteristics of these enzymes. Biomaterials have been designed that are responsive when the destructive enzymes MMPs are increased or have the activities of the antioxidant enzymes that play a protective role in arthritis. Here, we summarize recent studies on biomaterials associated with MMPs and antioxidant enzymes involved in the pathological process of arthritis. These enzyme-related biomaterials have been shown to be beneficial for arthritis treatment, but there are still some problems that need to be solved to improve efficacy, especially penetrating the deeper layer of articular cartilage and targeting osteoclasts in subchondral bone. In conclusion, enzyme-related nano-therapy is challenging and promising for arthritis treatment.

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