Chondrocyte senescence is an important pathogenic factor causing osteoarthritis (OA) progression through persistently producing pro-inflammatory factors. Mesenchymal stem cells-derived small extracellular vesicles (MSC-sEVs) have shown anti-inflammatory effects in OA models, while persistent existence of senescent chondrocytes still promotes cartilage destruction. Therefore, improving the targeted elimination ability on senescent chondrocytes is required to facilitate the translation of MSC-sEVs in OA treatment. In this study, versatile engineered MSC-sEVs are developed to targetedly clear senescent chondrocytes and maintain cartilage metabolic homeostasis. Specifically, MSC-sEVs are loaded with siRNA mouse double minute 2 homologue (siMDM2) and modified with cartilage-targeting peptide WYRGRL-PEG