Abstract
Osteoarthritis (OA) is a common chronic inflammatory disorder and a major cause of disability. Previous studies have shown that M1 macrophages play an important role in promoting increased inflammation in OA. And because the activated M1 macrophages highly expresses folate receptors, folate (FA) modified nanoparticles provide a new method for targeted drug delivery to macrophages. In this study, we reported itaconic acid (ITA) loaded nanoparticles encapsulated in FA modified cell membranes (FMINPs) as a potential therapeutic agent for OA treatment. This negative charged system has a core-shell structure with a particle size of 162.3 ± 3.65 nm and the system could slowly release ITA within 7 days. The cellular uptake of nanoparticles increased after FA modification. Importantly, the nanoparticles could inhibit the pyroptosis behavior of M1 macrophages by reducing the activity of NLRP3/capase-1/GSDMD protein, thereby alleviating the inhibitory effect of inflammatory microenvironment on mesenchymal stem cells (MSCs) activity and chondrogenic differentiation. Intra-articular injection of nanoparticles protected joint cartilage against OA development and reduced inflammatory response in the OA rat model. All in all, as a potential therapeutic agent, this system can target FA receptor for OA treatment, and the NLRP3/capase-1/GSDMD axis is indicated as an underlying mechanism of destructive cartilage disorders.
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