Copper silicate nanoparticle-mediated delivery of astragaloside-IV for osteoarthritis treatment by remodeling the articular cartilage microenvironment.

With the increasing global aging population, osteoarthritis (OA) has emerged as a major public health concern. OA pathogenesis is characterized by a complex interplay among inflammatory cytokines, reactive oxygen species, and extracellular matrix components, leading to cartilage degradation. Astragaloside-IV (AS-IV), a natural antioxidant, has shown promise in alleviating OA symptoms but is limited by poor bioavailability and ineffective cartilage drug delivery. To address these challenges, we aimed to develop a drug delivery system using copper silicate nanoparticles modified with polyethylene glycol and loaded with AS-IV (referred to as CSP@AS-IV). This system uses mesoporous silica nanoparticles with a hybrid metal framework to enhance drug release and efficacy. CSP@AS-IV degrades in the acidic OA microenvironment, releasing copper ions (Cu2+) and AS-IV, which synergistically exert antioxidant, antibacterial, anti-inflammatory, and chondroprotective effects. Both in vitro and in vivo rat model experiments demonstrated that CSP@AS-IV significantly alleviated joint inflammation, downregulated inflammatory marker expression, and promoted cartilage repair. These findings underscore that CSP@AS-IV offers considerable clinical potential for enhancing OA treatment outcomes.