Natural product curcumin-based coordination nanoparticles for treating osteoarthritis via targeting Nrf2 and blocking NLRP3 inflammasome

Oxidative stress leads to chondrocyte apoptosis and extracellular matrix (ECM) degradation, thus contributing to the pathogenesis of osteoarthritis (OA). Herein, curcumin with remarkable antioxidant and anti-inflammatory activities has been employed as an organic ligand to coordinate ferric ions for enhancing the water-solubility and biocompatibility of natural product curcumin. The obtained iron-curcumin-based coordination nanoparticles (Fe-Cur NPs) exhibit great water-solubility and efficient reactive oxygen/nitrogen species (ROS/RNS) scavenging ability. In vitro chondrocyte evaluation experiments indicated that the intracellular ROS/RNS induced by interleukin 1β (IL-1β) could be efficiently scavenged by these Fe-Cur NPs and oxidative-stress-induced cell death could be preserved as well. In addition, post intra-articular (i.a.) injection into OA rat joints, Fe-Cur NPs could greatly inhibit OA progression via activating the nuclear factor-erythroid 2 related factor-2 (Nrf2) and inhibiting nod-like receptor protein-3 (NLRP3) inflammasome activation in primary rat chondrocytes, as well as decrease the production of matrix degrading proteases and other inflammatory mediators. The efficient antioxidation and anti-inflammation performance of Fe-Cur NPs endow them as a promising nanoplatform for treatment of various inflammatory diseases, and more detailed researches will be conducted in the future.