Reactive oxygen species-responsive and scavenging polyurethane nanoparticles for treatment of osteoarthritis in vivo

Excessive reactive oxygen species (ROS) were closely associated with the progression of osteoarthritis (OA) in terms of symptoms and aggravation. To combine the advantages of ROS-stimuli responsiveness with scavenging ability, a novel polythioketal urethane (PTKU) was synthesized by simple and direct reaction between polythioketal (PTK) and diisocyanate. Apart from the excellent mechanical properties, the PTKU could be fabricated into various formulations, for example, nanoparticles (NPs) loaded with anti-inflammatory drug, dexamethasone. The [email protected] NPs were capable of scavenging several kinds of ROS, accompanying with the degradation of polymers. In vitro evaluation with macrophages revealed that the PTKU and [email protected] NPs had low cytotoxicity, and could suppress the intracellular ROS and expression of hypoxia inducible factor-1α (HIF-1α). Injection of the PTKU and [email protected] NPs to OA in vivo could significantly reduce the ROS level in articular cavity and alleviate destruction of oxidative stress, and resulted in a lower ratio of inflammatory M1 macrophages and a higher level of anti-inflammatory M2 macrophages. The synergistic effects of ROS-responsive drug delivery and ROS scavenging PTKU promoted significantly the therapeutic outcome of OA with a best score close to the normal cartilage, revealing the great promise of PTKU in treatment of OA in vivo.