The pH-responsive release profile of the nanoformulation, conducted in different buffers simulating physiological (pH 7.7) and osteoarthritic (pH 6.0) conditions, showed cumulative 6 release of 21.7% and 68.9%, respectively, after 150 min.6@HMSNs-Cs decreased the expression levels of IL-1β, TNF-α, IL-6, MMP-3 and MMP-13 up-regulated in IL-1β-stimulated rat chondrocytes by inhibiting the NF-κB pathway.In rats with MIA-induced knee OA, intra-articular injection of 6@HMSNs-Cs increased paw withdrawal threshold and ameliorated articular surface erosion and joint effusion. Here, MMP13 is linked to Joint swelling.