Tetrahedral Framework Nucleic Acid-Based Delivery of Astaxanthin Suppresses Chondrocyte Pyroptosis and Modulates Oxidative Stress for the Treatment of Osteoarthritis.

Worldwide, osteoarthritis (OA) is regarded as the most widespread, distressing, and limiting chronic disease affecting degenerative joints, and there is currently no disease-modifying treatment for OA. The pathogenesis of OA is significantly linked with oxidative stress and the process of pyroptosis. Astaxanthin (Ast) is a natural keto-carotenoid pigment with potent antioxidant activity and has been shown to effectively alleviate cartilage damage in OA. However, its poor water solubility and high sensitivity to light, temperature, and pH greatly limit its bioavailability. In this study, we developed Ast-loaded tetrahedral framework nucleic acids (tFNAs) for Ast delivery (TAC). Compared with free Ast and tFNAs, TAC exhibited improved drug stability and cellular uptake. Most importantly, TAC effectively protected chondrocytes against oxidative stress-induced pyroptosis, promoted extracellular matrix anabolism by chondrocytes, and ultimately alleviated cartilage damage in a rat DMM model. Thus, we believe that TACs hold great promise for the treatment of OA. This article is protected by copyright. All rights reserved.