Intra-articular delivery of anti-Hif-2α siRNA by chondrocyte-homing nanoparticles to prevent cartilage degeneration in arthritic mice

摘要: Hypoxia-inducible factor-2α (Hif-2α) is a potential therapeutic target for osteoarthritis (OA), but the application of this in delivery agents to chondrocytes remains challenge. A chondrocyte-targeting vector was constructed previous study enhance transfection efficiency and specificity vivo. This used vectors deliver small-interfering RNA (siRNA) silenced Hif-2α expression prevent cartilage degeneration OA-affected mice. After siRNA conducted by cartilage-targeting nanoparticles, protein levels Hif-2α, matrix metalloproteinases (MMP-13, -9), disintegrin metalloproteinase with thrombospondin motifs (ADAMTS-4, -5), vascular endothelial growth factor (VEGF), type X collagen nuclear (NF)-κB interleukin-1-beta (IL-1β)-stimulated were determined. Chondrocyte-targeting ability also determined fluorescein isothiocyanate (FITC)-labeled tracking under confocal microscope. OA model established surgically destabilizing knee joints mouse. then delivered intra-articularly nanoparticles Cartilage synovium inflammation analyzed histomorphometry. IL-1β synovial fluid measured enzyme-linked immunosorbent assay. In vitro assay results showed that catabolic factors, including MMP-13 -9, ADAMTS-4, VEGF, NF-κB, downregulated after Hif-2α-siRNA nanoparticles. vivo FITC-labeled confirmed promoted local concentration prolonged retention time cartilage. Histological analysis nanoparticle-mediated maintained integrity alleviated inflammation. decreased Thus, could specifically inhibit proteins.