A hyaluronic acid-coated mesoporous silica nanoplatform integrating platinum nanozymes and TGF-β inhibitor for synergistic disease-modifying osteoarthritis therapy

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by cartilage degradation, inflammation, and oxidative stress, with no effective disease-modifying therapies. Existing intra-articular (IA) treatments are limited by rapid clearance and an inability to simultaneously address the multifaceted OA pathology. To overcome these challenges, we developed a multifunctional mesoporous nanoplatform (mSiO 2 @Pt/SB@HA) for synergistic IA therapy. The platform features a mesoporous silica core (mSiO 2 ) for in situ growth of platinum nanoparticles (Pt NPs) and efficient loading of the TGF-β inhibitor SB-431542 (SB), coated with a hyaluronic acid (HA) shell. The HA coating ensures prolonged joint retention and responds to the OA microenvironment for controlled release. In vitro studies using chondrocytes confirmed that sustained SB release inhibits pathogenic TGF-β/Smad2/3 signaling, while the Pt NPs exert durable catalase (CAT)-like activity to scavenge reactive oxygen species (ROS). These actions synergistically disrupt the vicious cycle between oxidative stress and aberrant signaling that is strongly associated with OA progression. In vitro evaluations demonstrate that this integrated strategy achieves prolonged residence, targeted modulation of chondrocyte homeostasis and the OA pathological microenvironment, and effective cartilage protection, offering a promising disease-modifying approach for OA treatment.