Drug Delivery System Based on Near-Infrared Light-Responsive Molybdenum Disulfide Nanosheets Controls the High-Efficiency Release of Dexamethasone To Inhibit Inflammation and Treat Osteoarthritis.

Intra-articular injection has unique advantages in the treatment of osteoarthritis (OA), although it risks rapid clearance of the therapeutic drugs in the joint cavity. Combining therapeutic agents with functionalized nanocarriers may provide an effective solution. Controlling the therapeutic concentration of the drug in the joint cavity through the drug-loading nanosystem can synergistically treat OA. Here, we proposed an intra-articular drug delivery nanosystem MoS2@CS@Dex (MCD), using the chitosan (CS)-modified molybdenum disulfide (MoS2) nanosheets as near-infrared (NIR) photo-responsive carriers, loaded with the anti-inflammatory drug dexamethasone (Dex). MCD responded to NIR light both in vitro and in vivo and triggered Dex release through photothermal conversion. This enabled the remote-controlled Dex release in the joint cavity by adjusting the radiation behavior of the NIR light. MCD prolonged the residence time of Dex in the joint cavity. The intra-articular injection of MCD in combination with NIR radiation ensured a significant increase in the therapeutic effect of Dex at low systemic doses, which attenuated the cartilage erosion in the OA caused by the secretion of inflammatory factors including TNF-α and IL-1β. The toxicity and side effects on other internal organs during metabolism were reduced in the body. In addition, the photoacoustic imaging capability of MoS2 nanosheets was used to detect the metabolism of MCD in the joint cavity. Our research indicated that MCD has great potential to treat OA.