Multi-component Microcapsules Derived Spatiotemporal Sonodynamic Reinforcing Therapy against Rheumatoid Arthritis

Microcarriers have demonstrated substantial potential in therapeutic delivery for rheumatoid arthritis (RA) treatment. Herein, we propose a novel spatiotemporal ultrasound-responsive microcapsule carrier to reinforce curcumin-based sonodynamic therapy in treating RA. Based on microfluidic technology, microcapsules with a hydrogel shell loaded with curcumin and a perfluorocarbon core enriched with oxygen (CUR/O 2 -MCs) can be obtained. Ascribed to the liquid-to-gas transition property of perfluorocarbon and the sonosensitivity of curcumin, ultrasound stimulation can realize controlled oxygen release followed by sonodynamic reactive oxygen species production. We have demonstrated that the ultrasound-activated CUR/O 2 -MCs can elevate reactive oxygen species amounts in overproliferating fibroblast-like synoviocytes, subsequently inducing fibroblast-like synoviocyte apoptosis. In addition, the released curcumin and oxygen can bring about macrophage repolarization, antiangiogenesis, and hypoxia alleviation, which are also important in blocking RA progression. Thus, in collagen-induced arthritis rats, our spatiotemporal sonodynamic microcapsules can attenuate symptoms and reduce joint damage. These results indicate that our ultrasound-responsive multifunctional microcapsule is an ideal candidate for sonodynamic therapy enhancement and RA treatment.