Ultrasound-triggered perfluorocarbon-derived nanobombs for targeted therapies of rheumatoid arthritis

Abstract

Several kinds of therapeutic agents and methods are emerging to meet the increasing demand for a more effective rheumatoid arthritis (RA) therapy. However, developing an ultrasound (US)-responsive nanosystem for the treatment of RA is still filled with challenges. Herein, US-triggered perfluorocarbon (PFC)-based “nanobombs” are reported for the targeted treatment of RA. The targeted nanobombs were synthesized by a thin-film hydration and sonication method and had a core of perfluoropentane (PFP)-based nanodroplets (NDs) loaded with glucocorticoid dexamethasone (Dex) and a shell of folic acid (FA)-grafted polyethylene glycol (PEG)-functionalized phospholipid (PFP-Dex@NDs-PEG-FA). The 1 MHz US used as an initiator could trigger the “explosion” of nanobombs and enhance the drug release. The high concentration of PFP-Dex@NDs-PEG-FA with US showed the highest cytotoxicity on activated RAW264.7 cells, which were the main targeted cells in RA lesions, while the cellular uptake tests conducted on activated RAW264.7 cells demonstrated that the nanobombs modified with FA could increase the uptake of the activated RAW264.7 cells. Moreover, PFP-Dex@NDs-PEG-FA combined with US exhibited an excellent inhibition of synovitis and joint destruction in a collagen-induced arthritis SD rat model, acting as an efficient targeted agent for the RA therapy. Therefore, in this study, the targeted US-triggered PFC-based nanobombs with US used to treat the RA would offer a new treatment strategy and thus have a great potential for application in the areas of theranostic agents and nanomedicine treatment.