Macrophage membrane-encapsulated miRNA nanodelivery system for the treatment of hemophilic arthritis

Hemophilic arthritis (HA) is one of the most pathologically altered joint diseases. Specifically, periodic spontaneous hemorrhage-induced hyperinflammation of the synovium and irreversible destruction of the cartilage are the main mechanisms that profoundly affect the behavioral functioning and quality of life of patients. In this study, we isolated and characterized platelet-rich plasma-derived exosomes (PRP-exo). We performed microRNA (miRNA) sequencing and bioinformatics analysis on these exosomes to identify the most abundant miRNA, miR-451a. Following this, we developed an M@ZIF-8@miR nanotherapeutic system that utilizes nanoscale zeolitic imidazolate framework (ZIF) as a carrier for miRNA delivery, encapsulated within M2 membranes to enhance its anti-inflammatory effects. In vitro and in vivo studies demonstrated that M@ZIF-8@miR significantly reduced pro-inflammatory cytokines, controlled synovial inflammation, and achieved potent therapeutic efficacy by reducing joint damage. We suggest that the ability of M@ZIF-8@miR nanocomposites to inhibit pro-inflammatory cytokines, enhance cellular uptake, and exhibit good endosomal escape properties makes them promising carriers for the efficient delivery of therapeutic nucleic acid drugs. This approach delays joint degeneration and provides a promising combinatorial strategy for HA treatment.