Macrophages-mediated delivery of protoporphyrin for sonodynamic therapy of rheumatoid arthritis

[Display omitted] •Macrophages, which can migrate towards the inflammatory rheumatoid arthritis tissue under the guidance of cytokines, are used as carrier to enhance targeting effect.•Fe3O4 nanoparticles are used as primary carrier to increase loading capacity and realize synergistic ferroptosis/sonodynamic therapy.•Combined ferroptosis/sonodynamic therapy destructs the hyperplastic synovial cells and infiltrated inflammatory cells, demonstrating significant therapeutic effect for rheumatoid arthritis. Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by infiltration of inflammatory cells, hyperplasia of synovium, and destruction of the joint cartilage. Owing to the low drug delivery efficiency and limited immunosuppression effect, complete cure for RA remains a formidable challenge. Here, we show that live macrophages (Mφs) carrying protoporphyrin-loaded Fe3O4 nanoparticles can migrate to the RA tissues and inhibit the inflammation by sonodynamic therapy. The inflammation of RA leads to the release of cytokines, which guides the migration of the Mφs into the RA tissues, realizing precise delivery of therapeutics. The following sonodynamic therapy induced by ultrasound and protoporphyrin destructs the proliferating synovial cells and also infiltrated inflammatory cells, demonstrating significant therapeutic effect for RA. Meanwhile, the cytokines and relapse of RA can be remarkably suppressed because of the efficient damage to the resident inflammatory cells.