Related Experiment Video
Updated: Sep 7, 2026
Ameliorating Osteoarthritis in Mice Using Silver Nanoparticles
Published on: June 2, 2023
pH- and ROS-Responsive Polyurethane/Polylysine Nanomicelles Delivering Leonurine Attenuate Inflammation and Cartilage
1Department of Hand & Foot and Reconstructive Microsurgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People's Republic of China.
Purpose:
To develop a pH/ROS dual-responsive nanoplatform based on polyurethane (PU) and poly(L-lysine) (PLys) copolymers for targeted leonurine (Leo) delivery and to evaluate its anti-inflammatory and cartilage-protective effects in experimental rheumatoid arthritis (RA).
Methods:
PLys-modified PU polymers were grafted with 2,3-dimethylmaleic anhydride (DMMA) and incorporated with redox-cleavable thioether bonds to construct pH/ROS dual-responsive nanoparticles (PU-MA@Leo) through self-assembly. The physicochemical properties and stimulus-responsive behavior of the nanoparticles were evaluated under physiological and inflammatory conditions. Their anti-inflammatory and cartilage-protective effects were further assessed through in vitro and in vivo experiments, with a particular focus on macrophage-mediated inflammation, oxidative stress, inflammatory mediator production, and the JAK2/STAT3 signaling pathway.
Results:
PU-MA@Leo nanomicelles exhibited a leonurine drug-loading content of 21.17 ± 1.26% and an encapsulation efficiency of 63.85 ± 1.11%, compared with 17.60 ± 0.53% and 53.87 ± 0.96%, respectively, for PU@Leo. The formulations showed hemolysis rates below 1% and remained stable under physiological conditions. Acidic conditions induced DMMA cleavage and surface-charge conversion, whereas ROS exposure promoted thioether oxidation, micellar destabilization, and accelerated leonurine release. PU-MA showed enhanced uptake by activated macrophages. PU-MA@Leo reduced the expression of inflammatory mediators and was accompanied by decreased phosphorylation of JAK2 and STAT3. In the murine CIA model, rhodamine-labelled PU-MA micelles exhibited enhanced accumulation and fluorescence retention at arthritic joints. During the 27-day experimental period, PU-MA@Leo reduced arthritis severity and paw swelling and attenuated bone erosion, synovial inflammation, and cartilage damage compared with free leonurine and blank micelles.
Conclusion:
The pH/ROS-responsive PU-MA@Leo nanoplatform improved leonurine delivery to inflamed joints and demonstrated promising short-term anti-inflammatory and chondroprotective efficacy in murine experimental RA. These findings support further preclinical evaluation of this platform in human-relevant models, together with pharmacokinetic, biodistribution, long-term safety, immunogenicity, and post-treatment durability studies.