Antioxidant-Enhanced Nanoparticles Delay the Progression of Osteoarthritis

Osteoarthritis (OA) is an age-related degenerative disease. Oxidative stress (OS) regulates the pathogenesis of OA by affecting mitochondrial function. Mg²⁺ and citric acid can delay the progression of OA through reducing OS, but integrated therapy. In this study, a mesoporous nanoparticle (PCMg) composed of Mg²⁺, citric acid (CC), and dopamine was developed as a novel delivery platform. SS31, a positively charged peptide, was adsorbed onto the surface of PCMg through the charge interaction to obtain the new nanoparticle platform (PCMS). SS31 endowed PCMS with good biocompatibility and enabled it to be rapidly endocytosed by chondrocytes and simultaneously localized in mitochondria. In vitro, PCMS effectively reduced the reactive oxygen species (ROS) level and restored mitochondrial dysfunction mediated by <i>tert</i>-butyl hydroperoxide (TBHP) through reducing OS in chondrocytes. In addition, both in vivo and in vitro results demonstrated that PCMS had no malignant effect on chondrocyte viability and proliferation and was degradable. Through the destabilization of the medial meniscus (DMM) OA model, hematoxylin-eosin (HE), safranin, fast green (SO), and toluidine blue (TB) staining indicated that PCMS effectively alleviated the progression of OA. Comprehensive analysis indicated that PCMS treatment was an effective strategy for alleviating the progression of OA.