Amelioration of post-traumatic osteoarthritis via nanoparticle depots delivering small interfering RNA to damaged cartilage

The progression of osteoarthritis (OA) is associated with inflammation triggered by the enzymatic degradation of extracellular matrix in injured cartilage. Here, we show that a locally injected depot of nanoparticles functionalized with an antibody targeting collagen type-II and carrying small interfering RNA for matrix metalloproteinase 13 (MMP13), which breaks down collagen type-II, substantially reduced the expression of MMP13 and protected cartilage integrity and overall joint structure in acute and severe mouse models of post-traumatic OA. MMP13 inhibition suppressed clusters of genes associated with tissue restructuring, angiogenesis, innate immune responses and proteolysis. We also show that intra-articular injections of the nanoparticles led to higher reductions in disease progression than either a single injection or weekly injections of the steroid methylprednisolone. Sustained drug retention by targeting collagen in the damaged extracellular matrix of osteoarthritic cartilage may also be an effective strategy for the treatment of OA with other disease-modifying drugs.