Nanozyme-mediated redox and immune homeostasis in osteoarthritis and rheumatoid arthritis

Osteoarthritis (OA) and rheumatoid arthritis (RA) are inflammatory joint disorders that involve overlapping immune-cell populations with distinct etiologies. Key pathological features in the microenvironments of both OA and RA are redox imbalance, and dysregulated immune responses. From the perspective of pathological microenvironment, a high level of reactive oxygen species (ROS) triggers inflammatory cascades, shifting macrophage polarization to M1 (pro-inflammatory) phenotype, leading to cartilage erosion and tissue damage. Current therapeutics comprising anti-inflammatory drug and antioxidant agents provide symptomatic relief, yet possess significant challenges especially addressing interconnected axis (redox-immune axis). Nanozymes, catalytic nanomedicine with their enzyme-mimicking properties such as peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT), alongside with high stability, adjustable catalytic activities and adaptability to specific microenvironment, have emerged as promising platform in arthritis treatment to restore redox homeostasis and immune responses. Moreover, microenvironment-adaptive and combinational nanozymes systems further advance the targeted and multimodal therapeutic strategies in arthritis. This review highlights the pathological rationale for nanozymes in OA and RA, and explores nanozymes-immune crosstalk focusing on the redox homeostasis, immune regulation, and microenvironment-sensitive or combinational platforms. Furthermore, safety concerns regarding nanozymes treatment, and future avenue of the research are drawn to advance the nanozyme-based therapies on arthritis.