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Developing dedicated nanomedicines to improve delivery efficacy of anti-inflammatory drugs is still a formidable challenge. In this study, we present an extremely simple yet efficient approach to obtain hybrid nanodrugs through metal-drug coordination-driven self-assembly for carrier-free drug delivery. The resulting metallo-nanodrugs exhibit well-defined morphology and high drug encapsulation capability, allowing for the combination of magnetic resonance imaging and anti-inflammatory therapy. In the case of osteoarthritis (OA), the metallo-nanodrugs remarkably alleviate synovial inflammation, preventing cartilage destruction and extracellular matrix loss. In addition, it led to significantly improved therapeutic efficacy compared with intra-articular administration of the same dose of free drugs in OA mouse model. This work provides a very simple approach for the development of anti-inflammatory nanoformulations by exploiting coordination-driven self-assembly.

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