Ultrasound-Targeted Microbubble Destruction-Mediated Cell-Mimetic Nanodrugs for Treating Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease that mainly affects joints, and it can lead to disability and damage to vital organs if not diagnosed and treated in time. However, all current therapeutic agents for RA have limitations such as high dose, severe side effects, long-term use, and unsatisfactory therapeutic effects. The long-term use and dose escalation of methotrexate (MTX) may cause mild and severe side effects. To overcome the limitations, it is critical to target drug delivery to the inflamed joints. In this work, we constructed a folic acidtargeted and cell-mimetic nanodrug, MTX-loaded mesoporous silica composite nanoplatform (MMPRF), which can regulate drug release under ultrasound (US) and microbubble (MB) mediation. The targeted delivery and drug therapy were investigated through in vitro RAW264.7 cell experiments and in vivo collageninduced arthritis animal experiments. The result showed that the targeting ability to the joints of MMPRF was strong and was more significant after US and MB mediation, which can potently reduce joint swelling, bone erosion, and inflammation in joints. This work indicated that the US-and MB-mediated MMPRF not only would be a promising method for synergistic targeted treatment of RA but also may show high potential for serving as a nanomedicine for many other biomedical fields.

Sono-processes: Emerging systems and their applicability within the (bio-)medical field

“…Furthermore, MBs can be specifically functionalized or conjugated with ligands, such as antibodies, peptides, or aptamers, that bind to receptors or antigens on the surface of the target cell. The so called ‘US-targeted microbubble destruction’ (UTMD) is a promising field of research as cavitation of the MBs enables the local release of the payload of the MBs, therefore minimizes off-target effects, improves drug delivery efficiency and reduces systemic toxicity [200] , [201] , [202] . Li et al synthesized a liposome-MB system loaded with sinoporphyrin sodium, a sonosensitizer drug, to treat breast cancer.…”