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ROS-Targeted Nanomotor Therapy in OA: Cartilage Protection and Pain Relief
Meng Zheng1, Changyu Liu1, Qin Xia1
1Department of Orthopaedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Abstract:
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.
Insights
New Janus nanomotors deliver metformin directly to joints, targeting inflammation and pain in osteoarthritis (OA). These self-propelled nanomotors scavenge reactive oxygen species (ROS) and protect cartilage for improved arthritis management.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Pharmacology
Background:
- Osteoarthritis (OA) presents significant challenges due to limited effective treatments and the side effects of systemic drug administration.
- Current intra-articular injections for OA face issues with rapid clearance and poor tissue penetration, hindering therapeutic efficacy.
- Joint inflammatory pain is a major concern for OA patients, necessitating innovative pain management strategies.
Purpose of the Study:
- To develop novel nanozyme-based Janus nanomotors loaded with metformin (MET) for targeted reactive oxygen species (ROS)-mediated therapy in osteoarthritis.
- To leverage the self-propelling capabilities of nanomotors for enhanced deep tissue penetration and sustained drug delivery within the joint.
- To investigate the potential of these nanomotors in scavenging ROS, protecting chondrocytes, and alleviating joint pain.
Main Methods:
- Fabrication of nanozyme-based Janus nanomotors incorporating metformin (MET).
- Utilizing intrinsic superoxide dismutase (SOD) and catalase (CAT) activity to harness ROS as fuel for self-propulsion.
- Evaluating nanomotor penetration into cartilage and synovial tissue, ROS scavenging, MET release kinetics, and chondrocyte protection via NRF2/KEAP1 pathway modulation.
- Assessing the suppression of nociceptive signaling in dorsal root ganglia (DRG) to evaluate pain relief and mobility improvement.
Main Results:
- The developed nanomotors demonstrated self-propelled deep penetration into cartilage and synovial tissue, driven by ROS.
- Simultaneous ROS scavenging and sustained MET release were achieved, restoring redox homeostasis and protecting chondrocytes.
- Nanomotors effectively regulated the NRF2/KEAP1 signaling pathway, crucial for chondrocyte protection.
- Therapeutic intervention successfully suppressed nociceptive signaling in DRG, leading to significant joint pain alleviation and improved mobility.
Conclusions:
- Nanozyme-based Janus nanomotors offer a promising platform for targeted OA therapy by utilizing ROS as a fuel source.
- This approach enables efficient deep-tissue drug delivery, ROS scavenging, and chondrocyte protection, addressing key limitations of current OA treatments.
- The nanomotors provide a novel and effective strategy for managing osteoarthritis pain and protecting cartilage, paving the way for improved patient outcomes.