Abstract

Chronic inflammation in osteoarthritis (OA) elevates intracellular reactive oxygen species (ROS) and promotes the secretion of chemokines and inflammatory cytokines, thereby accelerating disease progression. Here, we engineered a sulfhydryl-modified hyaluronan (HA)-integrated selenium nanoparticles (HSe NPs) that enables targeted modulation of inflammatory responses in OA. Through covalent conjugation of sulfhydryl-modified HA with selenium nanoparticles, HSe NPs achieve enhanced structural stability and enable targeted delivery to IL-1β-stimulated chondrocytes via CD44 receptor-mediated endocytosis. Upon cellular uptake, HSe NPs selectively upregulate antioxidant selenoproteins, leading to efficient intracellular ROS scavenging and subsequent suppression of chemokine (CCL2, CXCL1) and pro-inflammatory cytokine (IL-6) secretion. In a rat OA model, HSe NPs not only mitigate cartilage matrix degradation and subchondral bone damage but also alleviate synovial inflammation by promoting M2 macrophage polarization. This CD44-targeted selenium nanoplatform, with its dual capacity for precise chondrocyte delivery and intracellular ROS neutralization, presents a simple yet effective strategy for treating inflammation-related diseases.