ROS-Targeted Nanomotor Therapy in OA: Cartilage Protection and Pain Relief.

Osteoarthritis (OA) is a prevalent degenerative joint disease with limited effective treatment options. Joint inflammatory pain is a primary reason patients seek care, but systemic drug administration often causes severe side effects, while intra-articular injection suffers from rapid clearance and poor tissue penetration. Herein, we develop nanozyme-based Janus nanomotors loaded with metformin (MET) for reactive oxygen species (ROS)-targeted therapy in OA. Leveraging intrinsic superoxide dismutase (SOD) and catalase (CAT) enzymatic activity, these nanomotors harness pathologically elevated ROS within the articular microenvironment as chemical fuel, achieving self-propelled deep penetration into both cartilage and synovial tissue. This mechanism facilitates simultaneous on-the-move ROS scavenging and sustained deep-tissue MET release, which further restores redox homeostasis and protects chondrocytes by regulating the NRF2/KEAP1 signaling pathway. Furthermore, the nanomotors can suppress nociceptive signaling in the dorsal root ganglia (DRG), thereby alleviating joint pain and improving mobility. This research offers a novel and efficient approach for cartilage protection and arthritis pain management.