Abstract
Osteoarthritis (OA) is a highly incident total joint degenerative disease with cartilage degeneration as the primary pathogenesis. The cartilage matrix is mainly composed of collagen, a matrix protein with a hallmark triple-helix structure, which unfolds with collagen degradation on the cartilage surface. A collagen hybridizing peptide (CHP) is a synthetic peptide that binds the denatured collagen triple helix, conferring a potential disease-targeting possibility for early-stage OA. Here, we constructed an albumin nanoparticle (An) conjugated with CHP, loaded with a chondrogenesis-promoting small molecule drug, kartogenin (KGN). The CHP-KGN-An particle exhibited sustained release of KGN in vitro and prolonged in vivo retention selectively within the degenerated cartilage in the knee joints of model mice with early-stage OA. Compared to treatment with KGN alone, CHP-KGN-An robustly attenuated cartilage degradation, synovitis, osteophyte formation, and subchondral bone sclerosis in OA model mice and exhibited a more prominent effect on physical activity improvement and pain alleviation. Our study showcases that targeting the degenerated cartilage by collagen hybridization can remarkably promote the efficacy of small molecule drugs and may provide a novel delivery strategy for early-stage OA therapeutics.