Carboxymethyl chitosan-assisted MnOx nanoparticles: Synthesis, characterization, detection and cartilage repair in early osteoarthritis

While the early detection and repair of cartilage lesions are crucial in the treatment of osteoarthritis (OA), they remain challenging because neither clinically used medicines nor magnetic resonance (MR) contrast agents can achieve detection and repair simultaneously. Here, we conjugated carboxymethyl chitosan (CMC) with a cartilage-targeting peptide (WYRGRL, termed WY) and then synthesized CMC-assisted manganese oxide nanoparticles (MnOx NPs). The resultant WY-CMC-MnOx NPs demonstrated an excellent biocompatibility and a good T1 relaxivity of 1.72 mM-1·s-1. Owing to their ultrasmall size and cartilage-targeting ability, the WY-CMC-MnOx NPs considerably increased the MR imaging quality of cartilage lesions compared to non-cartilage-targeting NPs. In contrast, clinically used gadolinium-diethylenetriamine pentaacetic acid (Gd-DPTA) failed to detect the cartilage lesions. Furthermore, WY-CMC-MnOx promoted chondrogenesis in mesenchymal stem cells, thereby enhancing OA therapy through efficient cartilage regeneration after intraarticularly injection in destabilization of medial meniscus (DMM) rat models. Our results indicate that WY-CMC-MnOx NPs are promising for use in the diagnosis and treatment of early OA.