Spatiotemporal sonodynamic therapy for the treatment of rheumatoid arthritis based on Z-scheme heterostructure sonosensitizer of HO-1 inhibitor jointed bismuth nanotriangle

Although some advances in rheumatoid arthritis (RA) clinical therapy, treatment discontinuation and suboptimal response to therapy are yet unresolved challenges. Sonodynamic therapy (SDT) has drawn great attention in bioapplications, owing to its superiorities such as non-invasiveness and better penetration depth. However, SDT efficiency is restricted by inefficient electron (e(-))-hole (h(+)) separation in sonosensitizer and O-2 deficiency in RA. In this study, we for the first time designed a Z-scheme heterostructure sonosensitizer based on bismuth nano triangles (Bi NTs) jointed heme oxygenase (HO-1) inhibitor (zinc protoporphyrin IX, ZnPP) with effective e(-)-h(+) separation capacity and high redox potentials. ZnPP would be pre-bonded to the overexpressed HO-1 in inflammatory joint fluid to suppress the antioxidant defense capability, thus reducing the ROS consumption. The nanoplatform could be activated by sono to achieve O-2 and ROS synchronous production. The obtained O-2 could alleviate hypoxia in inflamed joints to relieve synovial erosion and pannus. Then, the generated ROS could amplify the oxidative stress, which is associated with the release of cytochrome C, to trigger caspase-dependent apoptosis rather than necrosis to avoid further inflammation. The Z-scheme heterostructure Bi NTs-ZnPP/HSA overcomes the major obstacles of conventional sonosensitizer during the RA-SDT process and supplies a new strategy for RA treatment..

Automated summary

This study presents the design of a Z-scheme heterostructure sonosensitizer, which effectively separates electron-hole pairs and enhances redox potentials, thereby improving the efficiency of sonodynamic therapy. This novel sonosensitizer shows potential utility in the treatment of rheumatoid arthritis (RA).